Substituted terphenyl compounds for the treatment of inflammation

ABSTRACT

A class of terphenyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula II: ##STR1## wherein each of R 2  and R 3  is independently selected from hydrido and halo; or wherein R 2  and R 3  together form --OCH 2  O--; wherein each of R 6  through R 8  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, lower haloalkyl, and lower dialkylamino; or wherein R 6  and R 7  together form --OCH 2  O; and wherein R 12  is selected from lower alkylsulfonyl and aminosulfonyl; or a pharmaceutically-acceptable salt thereof.

FIELD OF THE INVENTION

This invention is in the field of anti-inflammatory pharmaceuticalagents and specifically relates to compounds, compositions and methodsfor treating inflammation and inflammation-associated disorders, such asarthritis.

BACKGROUND OF THE INVENTION

Prostaglandins play a major role in the inflammation process and theinhibition of prostaglandin production, especially production of PGG₂,PGH₂ and PGE₂, has been a common target of anti-inflammatory drugdiscovery. However, common non-steroidal anti-inflammatory drugs(NSAIDs) that are active in reducing the prostaglandin-induced pain andswelling associated with the inflammation process are also active inaffecting other prostaglandin-regulated processes not associated withthe inflammation process. Thus, use of high doses of most common NSAIDscan produce severe side effects, including life threatening ulcers, thatlimit their therapeutic potential. An alternative to NSAIDs is the useof corticosteroids, which have even more drastic side effects,especially when long term therapy is involved.

Previous NSAIDs have been found to prevent the production ofprostaglandins by inhibiting enzymes in the human arachidonicacid/prostaglandin pathway, including the enzyme cyclooxygenase (COX).The recent discovery of an inducible enzyme associated with inflammation(named "cyclooxygenase II (COX II)" or "prostaglandin G/H synthase II")provides a viable target of inhibition which more effectively reducesinflammation and produces fewer and less drastic side effects.

Substituted biphenyl compounds have been reported as components inphotographic materials. U.S. Pat. No. 5,238,790, to Shimura et al,describes the use of biphenyl compounds as dispersion agents inphotographic materials U.S. Pat. No. 5,294,530, to Seto et al, describesphotographic materials containing biphenyl compounds as anti-fadingagents.

U.S. Pat. No. 4,990,647, to Himmler et al, describes a method for thepreparation of unsymmetric biaryl compounds.

Substituted biphenyl compounds have been reported as having activity asangiotensin II antagonists. Heterocyclo-substituted biphenyl compoundsare described by D. Kim, et al Bioorg. Med. Chem. Lett., 4,41-44(1994)!. U.S. Pat. No. 5,254,546, to Ardecky et al, describestetrazole substituted biphenyl compounds. U.S. Pat. No. 5,240,928, toAllen et al, describes aminosulfonyl-substituted biphenyl compounds.

However, terphenyl compounds have not been previously described,especially as antiinflammatory agents.

DESCRIPTION OF THE INVENTION

A class of compounds useful in treating inflammation-related disordersis defined by Formula I: ##STR2## wherein each of R¹ through R⁴ isindependently selected from hydrido, halo, and alkoxy; wherein each ofR⁵ through R¹⁴ is independently selected from hydrido, alkyl, halo,alkoxy, alkylthio, cyano, haloalkyl, amino, alkylamino, dialkylamino,haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, aminosulfonyland alkylsulfonyl; or a pharmaceutically-acceptable salt thereof.

Compounds of Formula I would be useful for, but not limited to, thetreatment of inflammation in a subject, and for treatment of otherinflammation-associated disorders, such as, as an analgesic in thetreatment of pain and headaches, or as an antipyretic for the treatmentof fever. For example, compounds of Formula I would be useful to treatarthritis, including but not limited to rheumatoid arthritis,spondyloarthropathies, gouty arthritis, osteoarthritis, systemic lupuserythematosus and juvenile arthritis. Such compounds of Formula I wouldbe useful in the treatment of asthma, bronchitis, menstrual cramps,tendinitis, bursitis, and skin related conditions such as psoriasis,eczema, burns and dermatitis. Compounds of Formula I also would beuseful to treat gastrointestinal conditions such as inflammatory boweldisease, Crohn's disease, gastritis, irritable bowel syndrome andulcerative colitis and for the prevention of colorectal cancer.Compounds of Formula I would be useful in treating inflammation in suchdiseases as vascular diseases, migraine headaches, periarteritis nodosa,thyroiditis, aplastic anemia, Hodgkin's disease, sclerodoma, rheumaticfever, type I diabetes, myasthenia gravis, sarcoidosis, nephroticsyndrome, Behcet's syndrome, polymyositis, gingivitis, hypersensitivity,conjunctivitis, swelling occurring after injury, myocardial ischemia,and the like. The compounds are useful as antiinflammatory agents, suchas for the treatment of arthritis, with the additional benefit of havingsignificantly less harmful side effects.

The present invention preferably includes compounds which selectivelyinhibit cyclooxygenase II over cyclooxygenase I. Preferably, thecompounds have a cyclooxygenase II IC₅₀ of less than about 0.2-2 μM, andalso have a selectivity ratio of cyclooxygenase II inhibition overcyclooxygenase I inhibition of at least 50, and more preferably of atleast 100. Even more preferably, the compounds have a cyclooxygenase IIIC₅₀ of greater than about 1 μM, and more preferably of greater than 10μM. Such preferred selectivity may indicate an ability to reduce theincidence of common NSAID-induced side effects.

A preferred class of compounds consists of those compounds of Formula Iwherein each of R¹ through R⁴ is independently selected from hydrido andhalo; or wherein R² and R³ together form --OCH₂ O--; and wherein each ofR⁵ through R¹⁴ is independently selected from hydrido, lower alkyl,halo, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, amino,lower alkylamino, lower dialkylamino, lower haloalkoxy, lowerhydroxyalkyl, lower alkoxyalkyl, hydroxyl, mercapto, aminosulfonyl andlower alkylsulfonyl; or wherein R⁶ and R⁷ together form --OCH₂ O--.

A more preferred class of compounds consists of those compounds ofFormula I wherein each of R¹ through R⁴ is independently selected fromhydrido and halo; or wherein R² and R³ together form --OCH₂ O--; whereineach of R⁵ through R⁸ is independently selected from hydrido, loweralkyl, halo, lower alkoxy, lower haloalkyl, and lower dialkylamino; orwherein R⁶ and R⁷ together form --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ andR¹⁴ are hydrido; and wherein R¹² is selected from aminosulfonyl andlower alkylsulfonyl.

Within Formula I there is a subclass of compounds which consists ofcompounds wherein each of R¹ through R⁴ is independently selected fromhydrido and halo; or wherein R² and R³ together form --OCH₂ O--; whereineach of R⁵ and R⁹ is hydrido; wherein each of R⁶ through R⁸ isindependently selected from hydrido, lower alkyl, halo, lower alkoxy,lower haloalkyl, and lower dialkylamino; or wherein R⁶ and R⁷ togetherform --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and whereinR¹² is aminosulfonyl.

A class of compounds of particular interest consists of those compoundsof Formula I wherein each of R¹ through R⁴ is independently selectedfrom hydrido, fluoro, chloro and bromo; or wherein R² and R³ togetherform --OCH₂ O--; wherein each of R⁵ and R⁹ is hydrido; wherein each ofR⁶ through R⁸ is independently selected from hydrido, methyl, ethyl,fluoro, chloro, bromo, methoxy, ethoxy, propoxy, n-butoxy, fluoromethyl,difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl,trichloromethyl, pentafluoroethyl, heptafluoropropyl,difluorochloromethyl, dichlorofluoromethyl, difluoroethyl,difluoropropyl, dichloroethyl, dichloropropyl, N-ethyl-N-methylamino,N,N-dimethylamino, and N,N-diethylamino; or wherein R⁶ and R⁷ togetherform --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and whereinR¹² is aminosulfonyl.

Within Formula I there is a second subclass of compounds of highinterest wherein each of R¹ and R⁴ are hydrido; wherein each of R² andR³ is independently selected from hydrido and halo; or wherein R² and R³together form --OCH₂ O--; wherein each of R⁵ and R⁹ is hydrido; whereineach of R⁶ through R⁸ is independently selected from hydrido, loweralkyl, halo, and lower alkoxy; or wherein R⁶ and R⁷ together form --OCH₂O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and wherein R¹² is loweralkylsulfonyl.

A class of compounds of particular interest consists of those compoundsof Formula I wherein each of R¹ and R⁴ are hydrido; wherein each of R²and R³ is independently selected from hydrido, fluoro, chloro and bromo;or wherein R² and R³ together form --OCH₂ O--; wherein each of R⁵ and R⁹is hydrido; wherein each of R⁶ through R⁸ is independently selected fromhydrido, methyl, ethyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy,and n-butoxy; or wherein R⁶ and R⁷ together form --OCH₂ O--; whereinR¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and wherein R¹² is methylsulfonyl.

A family of specific compounds of particular interest within Formula Iconsists of compounds and pharmaceutically-acceptable salts thereof asfollows:

4- 2-biphenyl!benzenesulfonamide;

4- 2-(3-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(3-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(3-fluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3-chlorophenyl)phenyl!benzenesulfonamide;

4- 2-(3-tri fluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2- 3-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-(4-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(3,4-dimethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3-methoxy-4-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(3-chloro-4-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(4-methyl-3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2- 3-(N,N-dimethylamino)-4-methylphenyl!phenyl!benzenesulfonamide;

4- 2-4-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2-4-methoxy-3-methylphenyl)phenyl!benzenesulfonamide;

4- 2-3,4-dimethoxyphenyl)phenyl!benzenesulfonamide;

4- 2-3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2-3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide

4- 2-4-methoxy-3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2- 3-(N,N-dimethylamino)-4-methoxyphenyl!phenyl!benzenesulfonamide;

4- 2-(4-fluorophenyl)phenyl!benzenesulfonamide;

4- 2-(4-fluoro-3-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(4-fluoro-3-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(3,4-difluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide;

4- 2-(4-fluoro-3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2- 3-(N,N-dimethylamino)-4-fluorophenyl!phenyl!benzenesulfonamide;

4- 2-(4-chlorophenyl)phenyl!benzenesulfonamide;

4- 2-(4-chloro-3-methlphenyl)phenyl!benzenesulfonamide;

4- 2-(4-chloro-3-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(4-chloro-3-fluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3,4-dichlorophenyl)phenyl!benzenesulfonamide;

4- 2-(4-chloro-3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2- 4-chloro-3-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3-methyl-4-trifluoromethylphenyl)phenyl !benzenesulfonamide;

4- 2-(3-methoxy-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3-fluoro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3-chloro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2- 3,4-di(trifluoromethyl)phenyl!phenyl!benzenesulfonamide;

4- 2-3-(N,N-dimethylamino)-4-trifluoromethylphenyl!phenyl!benzenesulfonamide;

4- 2- 4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2- 4-(N,N-dimethylamino)-3-methylphenyl!phenyl!benzenesulfonamide;

4- 2- 4-(N,N-dimethylamino)-3-methoxyphenyl!phenyl!benzenesulfonamide;

4- 2- 4-(N,N-dimethylamino)-3-fluorophenyl!phenyl!benzenesulfonamide;

4- 2- 3-chloro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-4-(N,N-dimethylamino)-3-trifluoromethylphenyl!phenyl!benzenesulfonamide;

4- 2- 3,4-di (N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-(3,5-dimethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dimethoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-difluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dichlorophenyl)phenyl!benzenesulfonamide;

4- 2- 3,5-di(trifluoromethyl)phenyl!phenyl!benzenesulfonamide;

4- 2- 3,5-di(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-(3,4,5-trimethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dimethoxy-4-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-difluoro-4-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dichloro-4-methylphenyl)phenyl!benzenesulfonamide;

4- 2- 3,5-di(trifluoromethyl)-4-methylphenyl!phenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino)-4-methylphenyl!phenyl!benzenesulfonamide;

4- 2-(3,5-dimethyl-4-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(3,4,5-trimethoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-difluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dichloro-4-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2- 3,5-di(trifluoromethyl)-4-methoxyphenyl!phenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino)-4-methoxyphenyl!phenyl!benzenesulfonamide;

4- 2-(3,5-dimethyl-4-fluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dimethoxy-4-fluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3,4,5-trifluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dichloro-4-fluorophenyl)phenyl!benzenesulfonamide;

4- 2- 3,5-di(trifluoromethyl)-4-fluorophenyl!phenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino)-4-fluorophenyl!phenyl!benzenesulfonamide;

4- 2-(4-chloro-3,5-dimethylphenyl)phenyl!benzenesulfonamide;

4- 2-(4-chloro-3,5-dimethoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(4-chloro-3,5-difluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3,4,5-trichlorophenyl)phenyl!benzenesulfonamide;

4- 2- 4-chloro-3,5-di(trifluoromethyl!phenyl!phenyl!benzenesulfonamide;

4- 2-4-chloro-3,5-di(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-(3,5-dimethyl-4-(trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dimethoxy-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-difluoro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dichloro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2- 3,4,5-tri(trifluoromethyl)-phenyl!phenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino)-4-trifluoromethylphenyl!phenyl!benzenesulfonamide;

4- 2-3,5-dimethyl-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-3,5-dimethoxy-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-3,5-difluoro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-3,5-dichloro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-4-(N,N-dimethylamino)-3,5-di(trifluoromethyl)phenyl!phenyl!benzenesulfonamide;

4- 2- 3,4,5-tri(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 6-phenyl-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-chlorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,4-dimethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-fluoro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-chloro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-methoxy-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(4-methyl-3-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3-(N,N-dimethylamino)-4-methylphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-methoxy-3-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3-fluoro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-chloro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,4-dimethoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-)4-methoxy-3-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3-(N,N-dimethylamino)-4-methoxyphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-fluoro-3-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,4-difluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3-chloro-4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-fluoro-3-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(4-fluoro-3-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide

4- 6-3-(N,N-dimethylamino)-4-fluorophenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-chlorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-chloro-3-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-chloro-3-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,4-dichlorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-chloro-3-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(4-chloro-3-trifluoromethylphenyl)-1,3-benzodioxol5-yl!benzenesulfonamide;

4- 6-4-chloro-3-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3-methyl-4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3-fluoro-4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3-chloro-4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3-methoxy-4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,4-di(trifluoromethyl)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3-(N,N-dimethylamino)-4-trifluoromethylphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-(N,N-dimethylamino)-3-methylphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-(N,N-dimethylamino)-3-fluorophenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3-chloro-4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-(N,N-dimethylamino)-3-methoxyphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-(N,N-dimethylamino)-3-trifluoromethylphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,4-di((N,N-dimethylamino))phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,5-dimethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,5-difluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,5-dichlorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,5-dimethoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(trifluoromethyl)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dimethyl-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-difluoro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dichloro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dimethoxy-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(trifluoromethyl)-4-methylphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(N,N-dimethylamino)-4-methylphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dimethyl-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-difluoro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dichloro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dimethoxy-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(trifluoromethyl)-4-methoxyphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(N,N-dimethylamino)-4-methoxyphenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dimethyl-4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-difluoro-4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dichloro-4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dimethoxy-4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(trifluoromethyl)-4-fluorophenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(N,N-dimethylamino)-4-fluorophenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(4-chloro-3,5-dimethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(4-chloro-3,5-difluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-(3,4,5-trichlorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(4-chloro-3,5-dimethoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-chloro-3,5-di(trifluoromethyl)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-chloro-3,5-di(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dimethyl-4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-difluoro-4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dichloro-4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4-6-(3,5-dimethoxy-4-trifluoromethylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,4,5-tri(trifluoromethyl)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-di(N,N-dimethylamino)-4-trifluoromethylphenyl!1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-dimethyl-4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-(N,N-dimethylamino)-3,5-difluorophenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-dichloro-4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,5-dimethoxy-4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-4-(N,N-dimethylamino)-3,5-di(trifluoromethyl)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 6-3,4,5-tri(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;

4- 4,5-difluoro-2-biphenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3-methylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3-fluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3-chlorophenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3-methoxyphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,4-dimethylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide;

4- 2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3-methoxy-4-methylphenyl)phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(4-methyl-3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3-(N,N-dimethylamino)-4-methylphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(4-methoxyphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(4-methoxy-3-methylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;

4- 2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,4-dimethoxyphenyl)phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(4-methoxy-3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3-(N,N-dimethylamino)-methoxyphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(4-fluoro-3-methylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(4-fluoro-3-methoxyphenyl)phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(4-fluoro-3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3-(N,N-dimethylamino)-4-fluorophenyl!phenyl!benzenesulfonamide;

4- 2-(4-chlorophenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 2-(4-chloro-3-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 2-(4-chloro-3-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 2-(3,4-dichlorophenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 2-(4-chloro-3-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4-2-(4-chloro-3-trifluoromethylphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 2-4-chloro-3-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3-methyl-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3-fluoro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4-2-(3-chloro-4-trifluoromethylphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3-methoxy-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,4-di(trifluoromethyl)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3-(N,N-dimethylamino)-4-trifluoromethylphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-methylphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-fluorophenyl!phenyl!benzenesulfonamide;

4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!-4-difluorophenyl!benzenesulfonamide;

4- 4 ,5-difluoro-2-4-(N,N-dimethylamino)-3-methoxyphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-trifluoromethylphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,4-di(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide

4- 4,5-difluoro-2-(3,5-dimethylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,5-difluorophenyl)phenyl!benzenesulfonamide;

4- 2-(3,5-dichlorophenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,5-dimethoxyphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(trifluoromethyl)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,4,5-trimethylphenyl)phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-difluoro-4-methylphenyl)phenyl!benzenesulfonamide;

4-2-(3,5-dichloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-dimethoxy-4-methylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(trifluoromethyl)-4-methylphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(N,N-dimethylamino)-4-methylphenyl!phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-dimethyl-4-methoxyphenyl)phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-difluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;

4-2-(3,5-dichloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,4,5-trimethoxyphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(trifluoromethyl)-4-methoxyphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(N,N-dimethylamino)-4-methoxyphenyl!phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-dimethyl-4-fluorophenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,4,5-difluorophenyl)phenyl!benzenesulfonamide;

4-2-(3,5-dichloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-dimethoxy-4-fluorophenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(trifluoromethyl)-4-fluorophenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(N,N-dimethylamino)-4-fluorophenyl!phenyl!benzenesulfonamide;

4-2-(4-chloro-3,5-dimethylphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4-2-(4-chloro-3,5-difluorophenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 4,5-difluoro-2-(3,4,5-trichlorophenyl)phenyl!benzenesulfonamide;

4-2-(4-chloro-3,5-dimethoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4- 2-4-chloro-3,5-di(trifluoromethyl)phenyl!-4,5-difluorophenyl!benzenesulfonamide;

4- 2-4-chloro-3,5-di(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-dimethyl-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-difluoro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4-2-(3,5-dichloro-4-trifluoromethylphenyl)-4,5-difluorophenyl!benzenesulfonamide;

4-4,5-difluoro-2-(3,5-dimethoxy-4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,4,5-tri(trifluoromethyl)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(N,N-dimethylamino)-4-trifluoromethylphenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-dimethyl-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-difluoro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 2-3,5-dichloro-4-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-dimethoxy-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,5-di(trifluoromethyl)-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 4,5-difluoro-2-3,4,5-tri((N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;

4- 3,4,5,6-tetrafluoro-2-biphenyl!benzenesulfonamide;

4- 2-(3-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3-fluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3-chlorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-3,4,5,6-tetrafluoro-2-(3-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4- 2-3-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(4-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3,4-dimethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-fluoro-4-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-chloro-4-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-methoxy-4-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-methyl-3-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3-(N,N-dimethylamino)-4-methylphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(4-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-methyl-4-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-fluoro-4-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-chloro-4-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3,4-dimethoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-methoxy-3-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3-(N,N-dimethylamino)-4-methoxyphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(4-fluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-fluoro-3-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3,4-difluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-chloro-4-fluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-fluoro-3-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-fluoro-3-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3-(N,N-dimethylamino)-4-fluorophenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(4-chlorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-chloro-3-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-chloro-3-fluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3,4-dichlorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-chloro-3-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-chloro-3-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-4-chloro-3-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-3,4,5,6-tetrafluoro-2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide;

4-2-(3-methyl-4-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-fluoro-4-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-chloro-4-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3-methoxy-4-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,4-di(trifluoromethyl)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2- 3-(N,N-dimethylamino)-4-trifluoromethylphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-4-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-4-(N,N-dimethylamino)-3-methylphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-4-(N,N-dimethylamino)-3-fluorophenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-4-N,N-dimethylamino)-3-methoxyphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-4-(N,N-dimethylamino)-3-trifluoromethylphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,4-di(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3,5-dimethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3,5-difluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3,5-dichlorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(3,5-dimethoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(trifluoromethyl)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,4,5-trimethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-difluoro-4-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dichloro-4-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dimethoxy-4-methylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(trifluoromethyl)-4-methylphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino)-4-methylphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dimethyl-4-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-difluoro-4-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dichloro-4-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,4,5-trimethoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(trifluoromethyl)-4-methoxyphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino!-4-methoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dimethyl-4-fluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,4,5-trifluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dichloro-4-fluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dimethoxy-4-fluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(trifluoromethyl)-4-fluorophenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino)-4-fluorophenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-chloro-3,5-dimethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(4-chloro-3,5-difluorophenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-3,4,5,6-tetrafluoro-2-(3,4,5-trichloro-4-chlorophenyl)phenyl!benzenesulfonamide;

4-2-(4-chloro-3,5-dimethoxyphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-4-chloro-3,5-di(trifluoromethyl)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-4-chloro-3,5-di(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dimethyl-4-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-difluoro-4-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dichloro-4-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4-2-(3,5-dimethoxy-4-trifluoromethylphenyl)-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,4,5-tri(trifluoromethyl)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(N,N-dimethylamino)-4-trifluoromethylphenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-dimethyl-4-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-difluoro-4-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-dichloro-4-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-dimethoxy-4-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,5-di(trifluoromethyl)-4-(N,N-dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-3,4,5-tri(dimethylamino)phenyl!-3,4,5,6-tetrafluorophenyl!benzenesulfonamide;

4- 2-(4-hydroxymethylphenyl)phenyl!benzenesulfonamide;

4- 2-(4-methylthiophenyl)phenyl!benzenesulfonamide;

4- 2-(4-cyanophenyl)phenyl!benzenesulfonamide;

4- 2-(4-aminophenyl)phenyl!benzenesulfonamide;

4- 2-(4-hydroxyphenyl)phenyl!benzenesulfonamide;

4- 2- 4-(N-methylamino)phenyl!phenyl!benzenesulfonamide; and

4- 2-(4-methoxymethylphenyl)phenyl!benzenesulfonamide.

A second family of specific compounds of particular interest withinFormula I consists of compounds and pharmaceutically-acceptable saltsthereof as follows:

2- 4-(methylsulfonyl)phenyl!-1-phenylbenzene;

1-(3-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-chlorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,4-dimethylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-methoxy-4-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-fluoro-4-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-chloro-4-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-methyl-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,4-dimethoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-fluoro-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-chloro-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-fluoro-3-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-fluoro-3-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,4-difluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3-chloro-4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-chlorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-chloro-3-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-chloro-3-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-chloro-3-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,4-dichlorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dimethylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dimethoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-difluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dichlorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,4,5-trimethylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dimethoxy-4-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-difluoro-4-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dichloro-4-methylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dimethyl-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3 4,5-trimethoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-difluoro-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dichloro-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dimethyl-4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dimethoxy-4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,4,5-trifluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(3,5-dichloro-4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-chloro-3,5-dimethylphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-chloro-3,5-dimethoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-(4-chloro-3,5-difluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

1-3,4,5-trichlorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;

6- 4-(methylsulfonyl)phenyl!-1-phenyl-1,3-benzodioxole;

1-(3-methylphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-fluorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-chlorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-methoxyphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-methylphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,4-dimethylphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-fluoro-4-methylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-chloro-4-methylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-methoxy-4-methylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-methoxyphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-methyl-4-methoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-fluoro-4-methoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-chloro-4-methoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,4-dimethoxyphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-fluorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-fluoro-3-methylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,4-difluorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3-chloro-4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-fluoro-3-methoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-4-chlorophenyl)-6- 4-(methylsulfonyl)Phenyl!-1,3-benzodioxole;

1-4-chloro-3-methylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-4-chloro-3-fluorophenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,4-dichlorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-chloro-3-methoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dimethylphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-difluorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dichlorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dimethoxyphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3 4,5-trimethylphenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-difluoro-4-methylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dichloro-4-methylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dimethoxy-4-methylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dimethyl-4-methoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-difluoro-4-methoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dichloro-4-methoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3 4,5-trimethoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dimethyl-4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,4,5-trifluorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dichloro-4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,5-dimethoxy-4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-chloro-3,5-dimethylphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-chloro-3,5-difluorophenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(3,4,5-trichlorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1-(4-chloro-3,5-dimethoxyphenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;

1,2-difluoro-5- 4-(methylsulfonyl)phenyl!-4-phenylbenzene;

1,2-difluoro-4-(3-methylphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3-fluorophenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

4-(3-chlorophenyl)-1,2-difluoro-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3-methoxyphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(4-methylphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,4-dimethylphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3-fluoro-4-methylphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

4-(3-chloro-4-methylphenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3-methoxy-4-methylphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(4-methoxyphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(4-methoxy-3-methylphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3-fluoro-4-methoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

4-(3-chloro-4-methoxyphenyl)-1,2-difluoro-5-4-(memhylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,4-dimethoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(4-fluorophenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(4-fluoro-3-methylphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,4-difluorophenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

4-(3-chloro-4-fluorophenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(4-fluoro-3-methoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

4-(4-chlorophenyl)-1,2-difluoro-5- 4-(methylsulfonyl)phenyl!benzene;

4-(4-chloro-3-methylphenyl)-1,2-difluoro5-4-(methylsulfonyl)phenyl!benzene;

4-(4-chloro-3-fluorophenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

4-(3,4-dichlorophenyl)-1,2-difluoro-5- 4-(methylsulfonyl)phenyl!benzene;

4-(4-chloro-3-methoxyphenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,5-dimethylphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,5-difluorophenyl)-5- 4-(methylsulfonyl)phenyl!benzene;

4-(3,5-dichlorophenyl)-1,2-difluoro-5- 4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,5-dimethoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,4,5-trimethylphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,5-difluoro-4-methylphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

4-(3,5-dichloro-4-methylphenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,5-dimethoxy-4-methylphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,5-dimethyl-4-methoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,5-difluoro-4-methoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

4-(3,5-dichloro-4-methoxyphenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,4,5-trimethoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;

4-(3,5-dimethyl-4-fluorophenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,4,5-trifluorophenyl)-5-4-(methylsulfonyl)phenyl!benzene;

4-(3,5-dichloro-4-fluorophenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,5-dimethoxy-4-fluorophenyl)-5-4-(methylsulfonyl)phenyl!benzene;

4-(4-chloro-3,5-dimethylphenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

4-(4-chloro-3,5rs-difluorophenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene;

1,2-difluoro-4-(3,4,5-trichlorophenyl)-5-4-(methylsulfonyl)phenyl!benzene; and

4-(4-chloro-3,5-dimethoxyphenyl)-1,2-difluoro-5-4-(methylsulfonyl)phenyl!benzene.

Within Formula I there is a subclass of compounds of high interestrepresented by Formula II: ##STR3## wherein each of R² and R³ isindependently selected from hydrido and halo; or wherein R² and R³together form --OCH₂ O--; wherein each of R⁶ through R⁸ is independentlyselected from hydrido, lower alkyl, halo, lower alkoxy, lower haloalkyl,and lower dialkylamino; or wherein R⁶ and R⁷ together form --OCH₂ O--;and wherein R¹² is selected from lower alkylsulfonyl and aminosulfonyl;or a pharmaceutically-acceptable salt thereof.

Within Formula I there is a second subclass of compounds of highinterest represented by Formula III: ##STR4## wherein each of R⁶ throughR⁸ is independently selected from hydrido, halo, lower alkoxy, lowerhaloalkyl, amino, lower alkylamino, lower dialkylamino, and lowerhaloalkoxy; or wherein R⁶ and R⁷ together form --OCH₂ O--; or apharmaceutically-acceptable salt thereof.

The term "hydrido" denotes a single hydrogen atom (H). This hydridoradical may be attached, for example, to an oxygen atom to form ahydroxyl radical or two hydrido radicals may be attached to a carbonatom to form a methylene (--CH₂ --) radical. Where the term "alkyl" isused, either alone or within other terms such as "haloalkyl" and"alkylsulfonyl", it embraces linear or branched radicals having one toabout twenty carbon atoms or, preferably, one to about twelve carbonatoms. More preferred alkyl radicals are "lower alkyl" radicals havingone to about ten carbon atoms. Most preferred are lower alkyl radicalshaving one to about six carbon atoms. Examples of such radicals includemethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tertbutyl, pentyl, isoamyl, hexyl and the like. The term "halo" meanshalogens such as fluorine, chlorine, bromine or iodine atoms. The term"haloalkyl" embraces radicals wherein any one or more of the alkylcarbon atoms is substituted with halo as defined above. Specificallyembraced are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. Amonohaloalkyl radical, for one example, may have either an iodo, bromo,chloro or fluoro atom within the radical. Dihalo and polyhaloalkylradicals may have two or more of the same halo atoms or a combination ofdifferent halo radicals. "Lower haloalkyl" embraces radicals having 1-6carbon atoms. Examples of haloalkyl radicals include fluoromethyl,difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl,trichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl,difluorochloromethyl, dichlorofluoromethyl difluoroethyl,difluoropropyl; dichloroethyl and dichloropropyl. The term"hydroxyalkyl" embraces linear or branched alkyl radicals having one toabout ten carbon atoms any one of which may be substituted with one ormore hydroxyl radicals. More preferred hydroxyalkyl radicals are "lowerhydroxyalkyl" radicals having one to six carbon atoms and one or morehydroxyl radicals. Examples of such radicals include hydroxymethyl,hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl. The terms"alkoxy" and "alkoxyalkyl" embrace linear or branched oxy-containingradicals each having alkyl portions of one to about ten carbon atoms,such as methoxy radical. More preferred alkoxy radicals are "loweralkoxy" radicals having one to six carbon atoms. Examples of suchradicals include methoxy, ethoxy, propoxy, butoxy, tert-butoxy andmethylenedioxy. The term "alkoxyalkyl" also embraces alkyl radicalshaving two or more alkoxy radicals attached to the alkyl radical, thatis, to form monoalkoxyalkyl and dialkoxyalkyl radicals. More preferredalkoxyalkyl radicals are "lower alkoxyalkyl" radicals having one to sixcarbon atoms and one or two alkoxy radicals. Examples of such radicalsinclude methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl andmethoxypropyl. The "alkoxy" radicals may be further substituted with oneor more halo atoms, such as fluoro, chloro or bromo, to provide"haloalkoxy" radicals. Examples of such radicals include fluoromethoxy,chloromethoxy, trifluoromethoxy, trifluoroethoxy, fluoroethoxy andfluoropropoxy. The term "aryl", alone or in combination, means acarbocyclic aromatic system containing one, two or three rings whereinsuch rings may be attached together in a pendent manner or may be fused.The term "aryl" embraces aromatic radicals such as phenyl, naphthyl,tetrahydronaphthyl, indane and biphenyl. The term "heterocyclic"embraces saturated, partially saturated and unsaturatedheteroatom-containing ring-shaped radicals, where the heteroatoms may beselected from nitrogen, sulfur and oxygen. Examples of saturatedheterocyclic radicals include saturated 3 to 6-membered heteromonocylicgroup containing 1 to 4 nitrogen atoms e.g. pyrrolidinyl,imidazolidinyl, piperidino, piperazinyl, etc.!; saturated 3 to6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1to 3 nitrogen atoms e.g. morpholinyl, etc.!; saturated 3 to 6-memberedheteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3nitrogen atoms e.g., thiazolidinyl, etc.!. Examples of partiallysaturated heterocyclic radicals include dihydrothiophene, dihydropyran,dihydrofuran and dihydrothiazole. The term "heteroaryl" embracesunsaturated heterocyclic radicals. Examples of unsaturated heterocyclicradicals, also termed "heteroaryl" radicals include unsaturated 5 to 6membered heteromonocyclic group containing 1 to 4nitrogen atoms, forexample, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, 2-pyridyl,3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl e.g.,4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl,etc.!tetrazolyl e.g. 1H-tetrazolyl, 2H-tetrazolyl, etc.!, etc.;unsaturated condensed heterocyclic group containing 1 to 5 nitrogenatoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl,quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyle.g., tetrazolo 1,5-b!pyridazinyl, etc.!, etc.; unsaturated 3 to6-membered heteromonocyclic group containing an oxygen atom, forexample, pyranyl, 2-furyl, 3-furyl, etc.; unsaturated 5 to 6-memberedheteromonocyclic group containing a sulfur atom, for example, 2-thienyl,3-thienyl, etc.; unsaturated 5- to 6-membered heteromonocyclic groupcontaining 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example,oxazolyl, isoxazolyl, oxadiazolyl e.g., 1,2,4-oxadiazolyl1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.!etc.; unsaturated condensedheterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogenatoms e.g. benzoxazolyl, benzoxadiazolyl, etc.!; unsaturated 5 to6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl e.g.,1,2,4-thiadiazolyl, 1,3,4thiadiazolyl, 1,2,5-thiadiazolyl, etc.! etc.;unsaturated condensed heterocyclic group containing 1 to 2 sulfur atomsand 1 to 3 nitrogen atoms e.g., benzothiazolyl, benzothiadiazolyl, etc.!and the like. The term also embraces radicals where heterocyclicradicals are fused with aryl radicals. Examples of such fused bicyclicradicals include benzofuran, benzothiophene, and the like. Said"heterocyclic group" may have 1 to 3 substituents such as lower alkyl,hydroxy, oxo, amino and lower alkylamino. Preferred heterocyclicradicals include five to ten membered fused or unfused radicals. Morepreferred examples of heteroaryl radicals include benzofuryl,2,3-dihydrobenzofuryl, benzothienyl, indolyl, dihydroindolyl, chromanyl,benzopyran, thiochromanyl, benzothiopyran, benzodioxolyl, benzodioxanyl,pyridyl, thienyl, thiazolyl, oxazolyl, furyl, and pyrazinyl. The term"sulfonyl", whether used alone or linked to other terms such asalkylsulfonyl, denotes respectively divalent radicals --SO₂ --."Alkylsulfonyl" embraces alkyl radicals attached to a sulfonyl radical,where alkyl is defined as above. More preferred alkylsulfonyl radicalsare "lower alkylsulfonyl" radicals having one to six carbon atoms.Examples of such lower alkylsulfonyl radicals include methylsulfonyl,ethylsulfonyl and propylsulfonyl. The terms "sulfamyl," "aminosulfonyl"and "sulfonamidyl" denotes a sulfonyl radical substituted with an amineradical, forming a sulfonamide (--SO₂ NH₂). The terms "carboxy" or"carboxyl", whether used alone or with other terms, such as"carboxyalkyl", denotes --CO₂ H. The term "alkylthio" embraces radicalscontaining a linear or branched alkyl radical, of one to ten carbonatoms, attached to a divalent sulfur atom. An example of "alkylthio" ismethylthio, (CH₃ --S--). The terms "N-alkylamino" and "N,N-dialkylamino"denote amino groups which have been substituted with one alkyl radicaland with two alkyl radicals, respectively. More preferred alkylaminoradicals are "lower alkylamino" radicals having one or two alkylradicals of one to six carbon atoms, attached to a nitrogen atom.Suitable "alkylamino" may be mono or dialkylamino such as N-methylamino,N-ethylamino; N,N-dimethylamino, N,N-diethylamino or the like.

The present invention comprises a pharmaceutical composition for thetreatment of inflammation and inflammation-associated disorders, such asarthritis, comprising a therapeutically-effective amount of a compoundof Formula I in association with at least onepharmaceutically-acceptable carrier, adjuvant or diluent.

The present invention also comprises a therapeutic method of treatinginflammation or an inflammation-associated disorder in a subject, themethod comprising administering to a subject having or susceptible tosuch inflammation or inflammation associated disorder atherapeutically-effective amount of a compound of Formula I.

Also included in the family of compounds of Formula I are thepharmaceutically-acceptable salts thereof. The term"pharmaceutically-acceptable salts" embraces salts commonly used to formalkali metal salts and to form addition salts of free acids or freebases. The nature of the salt is not critical, provided that it ispharmaceutically-acceptable. Suitable pharmaceutically-acceptable acidaddition salts of compounds of Formula I may be prepared from aninorganic acid or from an organic acid. Examples of such inorganic acidsare hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuricand phosphoric acid. Appropriate organic acids may be selected fromaliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic,carboxylic and sulfonic classes of organic acids, example of which areformic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic,tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic,aspartic, glutamic, benzoic, anthranilic, mesylic, salicyclic,salicyclic, 4-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic),methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic,2-hydroxyethanesulfonic, toluenesulfonic, sulfanilic,cyclohexylaminosulfonic, stearic, algenic, β-hydroxybutyric, salicyclic,galactaric and galacturonic acid. Suitable pharmaceutically-acceptablebase addition salts of compounds of Formula I include metallic saltsmade from aluminum, calcium, lithium, magnesium, potassium, sodium andzinc or organic salts made from N,N'-dibenzylethylenediamine,chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine(N-methylglucamine) and procaine. All of these salts may be prepared byconventional means from the corresponding compound of Formula I byreacting, for example, the appropriate acid or base with the compound ofFormula I.

General Synthetic Procedures

The compounds of the invention can be synthesized according to thefollowing procedures of Schemes I-XI, wherein the R¹ -R¹⁴ substituentsare as defined for Formula I, above, except where further noted.##STR5##

Synthetic Scheme I shows the three step procedure for the preparation ofthe prerequisite substituted phenylboronic acids 1 and 2 fromcommercially available phenyl bromides. In step one, halogen-metalinterchange in THF at -78° C. generates the corresponding organolithiumreagents. In step two, the organolithium species are reacted withtrimethyl borate to give the corresponding methyl esters. In step three,hydrolysis with aqueous sodium hydroxide provides the substitutedphenylboronic acids 1 and 2, respectively. ##STR6##

Synthetic Scheme II shows an alternative three step procedure for thepreparation of the prerequisite substituted phenylboronic acids 1 and 2from commercially available phenyl bromides. In step one, reaction withmagnesium metal in THP at reflux in the presence of an iodine catalystgenerates the corresponding Grignard reagents. In step two, the Grignardreagents are reacted with trimethyl borate to give the correspondingmethyl esters. In step three, hydrolysis with aqueous sodium hydroxideprovides the substituted phenylboronic acids 1 and 2, respectively.##STR7##

Synthetic Scheme III shows the procedure for the preparation of thesubstituted 2-bromo-biphenyl intermediates 3 from commercially available1,2-dibromobenzenes and the appropriate substituted phenylboronic acid1-(prepared in Synthetic Schemes I and II). Using a coupling proceduresimilar to the one developed by Suzuki et al. Synth. Commun., 11, 513(1981)!, 1,2-dibromobenzenes are reacted with 1 in toluene/ethanol atreflux in the presence of a Pd°. catalyst, e.g.,tetrakis(triphenylphosphine)palladium(O), and 2M sodium carbonate togive the corresponding substituted 2-bromobiphenyl intermediates 3.##STR8##

Synthetic Scheme IV shows the procedure for the preparation of thesubstituted 2-bromobiphenyl intermediates 4 from commercially available1,2-dibromobenzenes and the appropriate substituted phenylboronic acids2-(prepared in Synthetic Schemes I and II). Using a coupling proceduresimilar to the one developed by Suzuki et al. (Synthetic Scheme III),1,2-dibromobenzenes are reacted with 2 in toluene/ethanol at reflux inthe presence of a Pd° catalyst, e.g., tetrakis(triphenylphosphine)palladium(O), and 2M sodium carbonate to give thecorresponding substituted 2-bromobiphenyl intermediates 4. ##STR9##

Synthetic Scheme V shows the procedure for the preparation of1,2-diarylbenzene antiinflammatory agents 5 from 2-bromo-biphenylintermediates 3-(prepared in Synthetic Scheme III) and the appropriatesubstituted phenylboronic acids 2-(prepared in Synthetic Schemes I andII). Using a coupling procedure similar to the one developed by Suzukiet al. (Synthetic Scheme III), intermediates 3 are reacted with 2 intoluene/ethanol at reflux in the presence of a Pd° catalyst, e.g.,tetrakis(triphenylphosphine)palladium(O), and 2M sodium carbonate togive the corresponding 1,2-diarylbenzene antiinflammatory agents 5 ofthis invention. ##STR10##

Synthetic Scheme VI shows the procedure for the preparation of1,2-diarylbenzene antiinflammatory agents 5 from 2-bromo-biphenylintermediates 4-(prepared in Synthetic Scheme IV) and the appropriatesubstituted phenylboronic acids 1-(prepared in Synthetic Schemes I andII). Using a coupling procedure similar to the one developed by Suzukiet al. (Synthetic Scheme III), intermediates 4 are reacted with 1 intoluene/ethanol at reflux in the presence of a Pd° catalyst, e.g.,tetrakis(triphenylphosphine)palladium(O), and 2M sodium carbonate togive the corresponding 1,2-diarylbenzene antiinflammatory agents 5 ofthis invention. ##STR11##

Synthetic Scheme VII shows an alternative one step procedure for thepreparation of 1,2-diarylbenzene antiinflammatory agents 5 fromcommercially available 1,2-dibromobenzenes and the appropriatesubstituted phenylboronic acids 1 and 2-(prepared in Synthetic Schemes Iand II). Using a coupling procedure similar to the one developed bySuzuki et al. (Synthetic Scheme III), an equimolar mixture of1,2-dibromobenzenes, 1 and 2 are reacted in toluene/ethanol at reflux inthe presence of a Pd° catalyst, e.g.,tetrakis(triphenylphosphine)palladium(O), and 2M sodium carbonate togive the corresponding 1,2-diarylbenzene antiinflammatory agents 5 ofthis invention. ##STR12##

Synthetic Scheme VIII shows the three step procedure for the preparationof the 2-arylphenylboronic acids 6 and 7 from corresponding2-bromobiphenyl intermediates 3-(prepared in Synthetic Scheme III) and4-(prepared in Synthetic Scheme IV), respectively. In step one,halogen-metal interchange in THP at -78° C. generates the correspondingorganolithium reagents. In step two, the organolithium species arereacted with trimethyl borate to give the corresponding methyl esters.In step three, hydrolysis with aqueous sodium hydroxide provides thesubstituted phenylboronic acids 6 and 7, respectively. ##STR13##

Synthetic Scheme IX shows the procedure for the preparation of1,2-diarylbenzene antiinflammatory agents 5 from commercially availablesubstituted phenyl bromides and 2-aryl-phenylboronic acids 6-(preparedin Synthetic Scheme VIII). Using a coupling procedure similar to the onedeveloped by Suzuki et al. (Synthetic Scheme III), substituted phenylbromides are reacted with 6 in toluene/ethanol at reflux in the presenceof a Pd° catalyst, e.g., tetrakis(triphenylphosphine)palladium(O), and2M sodium carbonate to give the corresponding 1,2-diarylbenzeneantiinflammatory agents 5 of this invention. ##STR14##

Synthetic Scheme X shows the procedure for the preparation of1,2-diarylbenzene antiinflammatory agents 5 from commercially availablesubstituted phenyl bromides and 2-aryl-phenylboronic acids 7-(preparedin Synthetic Scheme VIII). Using a coupling procedure similar to the onedeveloped by Suzuki et al. (Synthetic Scheme III), substituted phenylbromides are reacted with 7 in toluene/ethanol at reflux in the presenceof a Pd° catalyst, e.g., tetrakis(triphenylphosphine) palladium(O), and2M sodium carbonate to give the corresponding 1,2-diarylbenzeneantiinflammatory agents 5 of this invention. ##STR15##

Synthetic Scheme XI shows the three step procedure for the preparationof sulfonamide antiinflammatory agents 9 from their corresponding methylsulfones 8. Using a procedure similar to the one developed by Huang etal. Tetrahedron Lett., 35, 7201(1994)!, THF solutions of themethylsulfones 8 at -78° C. are treated with base, e.g., n-BuLi, n-C₃ H₇MgCl, etc., to generate the corresponding carbanions. In step two, theanions are treated with an organoborane, e.g., triethylborane,tributylborane, etc., at -78° C. and warmed to ambient temperature priorto stirring at reflux. In step three, an aqueous solution of sodiumacetate and hydroxyamine-O-sulfonic acid is added to provide thecorresponding sulfonamide antiinflammatory agents 9 (5 where R¹² =SO₂NH₂) of this invention.

The following examples contain detailed descriptions of the methods ofpreparation of compounds of Formulas I-II. These detailed descriptionsfall within the scope, and serve to exemplify, the above describedGeneral Synthetic Procedures which form part of the invention. Thesedetailed descriptions are presented for illustrative purposes only andare not intended as a restriction on the scope of the invention. Allparts are by weight and temperatures are in Degrees centigrade unlessotherwise indicated. HRMS is an abbreviation for High resolution massspectrometry. The term "ND" signifies "not determined."

EXAMPLE 1 ##STR16## Step 1 Preparation of1-bromo-2-(4-fluorophenyl)benzene

Under nitrogen, 1.2 g (1.0 mmol) of Pd(PPh₃)4 was added to a stirredsolution of 9.9 g (42 mmol) of 1,2-dibromobenzene (Aldrich) and 3.0 g(21 mmol) of 4-fluorophenylboronic acid in 42 mL of toluene, 42 mL ofethanol and 42 mL of 2M Na₂ CO₃. After vigorous stirring at reflux for 3hours, the solvent was removed in vacuo. The residue was dissolved inethyl acetate. The resulting solution was washed with water and driedover MgSO₄. Purification by silica gel chromatography (Waters Prep-500A)with hexane gave 4.35 g (81%) of 1-bromo-2-(4-fluorophenyl)benzene as acolorless oil: NMR (CDCl₃) δ 7.07-7.26 (m, 3H), 7.27-7.44 (m, 4H),7.67(d, J=8 Hz, 1H).

Step 2 Preparation of 4-methylthiophenylboronic acid

Under nitrogen, 113 mL (181 mmol) of n-BuLi (1.6M in hexanes) was addedto a stirred solution of 30 g (150 mmol) of 4-bromothioanisole(Lancaster) in 1,500 mL of anhydrous tetrahydrofuran (THF) at --78° C.After 30 minutes, 51 mL (450 mol) of trimethylborate was added. Thereaction was warmed to ambient temperature and stirred overnight. Theresulting solution was treated with 300 mL of 10% NaOH and stirredvigorously for 1 hour. The THF was removed in vacuo, the pH adjusted to4-5 and the solid collected by filtration. The solid was washedrepeatedly with water and hexane. Drying in vacuo gave 21 g (83%) of4-methylthiophenylboronic acid as a colorless solid: NMR (DMSO-d₆) δ2.47 (s, 3H), 7.20 (d, J=8 Hz, 2H), 7.71 (d, J=8 Hz, 2H), 7.96 s,

Step 3 Preparation of 1-(4-fluorophenyl)-2- 4-(methylthio)phenyl!benzene

Under nitrogen, 200 mg of Pd(PPh₃)₄ was added to a stirred solution of500 mg (2.0 mmol) of 1-bromo-2-(4-fluorophenyl)benzene (Step 1) and 500mg (3.0 mmol) of 4-methylthiophenylboronic acid (Step 2) in 7 mL oftoluene, 7 mL of ethanol and 7 mL of 2M Na₂ CO₃. After vigorous stirringat reflux overnight, the solvent was removed in vacuo. The residue wasdissolved in ethyl acetate. The resulting solution was washed with waterand dried over MgSO₄. Purification by silica gel chromatography (WatersLC-2000) with ethyl acetate/hexane (2:98) as the eluent gave 550 mg of1-(4-fluorophenyl)-2- 4-(methylthio)phenyl!benzene as a semi-solid: NMR(CDCl₃) δ 2.46 (s, 3H), 6.92 (t, J=8 Hz, 2H), 7.02-7.14 (m, 6H)7.37-7.42 (m, 4H). MS (EI): m/e (rel intensity) 294 (100), 279 (39), 277(56), 246 (74), 227 (40), 190 (43) 190 (38), 140 (44).

Step 4 Preparation of 1-(4-fluorophenyl)-2-4-(methylsulfonyl)phenyl!benzene

To a stirred solution of 550 mg (1.9 mmol) of crude1-(4-fluoro-phenyl)-2- 4-(methylthio)phenyl!benzene (Step 3) in 10 mL ofmethylene chloride at ambient temperature was slowly added 1.3 g (4.1mmol) of 3-chloroperoxybenzoic acid (ca. 55%). Stirring was continuedfor 20 minutes prior to the addition of 1 g of Na₂ SO₃. The reaction wasallowed to stir for an additional 10 minutes and the solvent removed invacuo. The residue was dissolved in ethyl acetate and the resultingsolution washed twice with saturated NaHCO3 and dried over MgSO₄.Recrystallization from ethyl acetate/hexane gave 437 mg (94%) of1-(4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene as a colorlesssolid: mp 178.0°-179.0° C.; NMR (CDCl₃) δ 3.05 (s, 3H), 6.93 (t, J=8 Hz,2H), 7.03-7.09 (m, 2H), 7.32 (d, J=8 Hz, 2H), 7.38-7.50 (m, 4H), 7.80(d, J=8 Hz, 2H). MS (FAB): m/e 333 (M+Li). Anal. Calc'd for C₁₉ H₁₅ FO₂S: C, 69.86; H, 4.60; F, 5.79. Found: C, 69.74; H, 4.72; F, 5.51.

EXAMPLE 2 ##STR17## Step 1 Preparation of2-(4-fluorophenyl)phenylboronic acid

Following the general procedure outlined in Synthetic Scheme VIII, 4.35g (17.3 mmol) of 1-bromo-2-(4-fluorophenyl)benzene (Example 1, Step 1)was converted to 2-(4-fluorophenyl)phenylboronic acid: NMR (CDCl₃) δ4.27 (s, 2H), 7.09-7.20 (m, 2H), 7.25-7.32 (m, 1H), 7.34-7.53 (m, 4H),7.90 (d, J=8 Hz, 1H).

Step 2 Preparation of 4- 2-(4-fluorophenol)phenyl!benzenesulfonamide

Following the general procedure outlined in Synthetic Scheme IX, 1.5 g(6.9 mmol) of 2-(4-fluorophenyl)phenylboronic acid (Step 1) was reactedwith 2.5 g (10.4 mmol) of 4-bromobenzenesulfonamide (Lancaster).Purification by silica gel chromatography (Waters LC-2000) with ethylacetate/hexane (3:7) and subsequent recrystallization from ethylacetate/hexane gave 1.04 g (46%) of 4- 2-(4-fluorophenyl)phenyl!benzenesulfonamide as a colorless solid: mp 187.3--188.2° C.; NMR(CDCl₃) δ 4.83 (s, 2H), 6.92 (t, J=9 Hz, 2H), 7.02-7.11 (m, 2H), 7.27(d, J=9 Hz, 2H), 7.36-7.50 (m, 4H), 7.78 (d, J=8 Hz, 2H). MS (EI): m/e(rel intensity) 327 (75) 245 (100); HRMS Calc'd for C₁₈ H₁₄ FNO₂ S:327.0729. Found: 327.0743. Anal. Calc'd for C₁₈ H₁₄ FNO₂ S: C, 66.04; H,4.31; N, 4.28.

Found: C, 65.86; H, 4.51; N, 4.34.

EXAMPLE 3 ##STR18## Step 1 Preparation of1-bromo-2-(4-chlorophenyl)benzene

Following the general procedure outlined in Synthetic Scheme III, 9.0 g(38 mmol) of 1,2-dibromobenzene was reacted with 3.0 g (19 mmol) of4-chlorophenylboronic acid (Lancaster). Purification by silica gelchromatography (Waters Prep-500A) with hexane gave 4.39 g (84%) of1-bromo-2-(4-chlorophenyl)benzene as a colorless oil: NMR (CDCl₃) δ7.18-7.26 (m, 1H), 7.28-7.44 (m, 6H), 7.68 (dd, J=1.5, 8 Hz, 1H).

Step 2 Preparation of 2-(4-chlorophenyl)phenylboronic acid

Following the general procedure outlined in Synthetic Scheme VIII, 4.39g (16.4 mmol) of 1-bromo-2-(4chlorophenyl)benzene (Step 1) was convertedto 2-(4chlorophenyl)phenylboronic acid: NMR (CDCl₃) δ 4.20 (s, 2H),7.19-7.55 (m, 7H), 7.89 (d, J=8 Hz, 1H).

Step 3 Preparation of 4- 2-(4-chlorophenyl)phenyl!benzenesulfonamide

Following the general procedure outlined in Synthetic Scheme IX, 1.6 g(6.9 mmol) of 2-(4-chlorophenyl)phenylboronic acid (Step 2) was reactedwith 1.8 g (7.6 mmol) of 4-bromobenzenesulfonamide. Purification bysilica gel chromatography (Waters LC-2000) with ethyl acetate/hexane(3:7) and subsequent recrystallization from ethyl acetate/hexane gave1.59 g (67%) of 4- 2-(4-chlorophenyl)phenyl!benzenesulfonamide as acolorless solid: mp 206.2°-207.0° C.; NMR (CDCl₃) δ 4.77 (s, 2H), 7.04(d, J=9 Hz, 2H), 7.16-7.31 (m, 4H), 7.36-7.51 (m, 4H), 7.80(d, J=9 Hz,2H). MS (EI): m/e (rel intensity) 343 (100), 308 (13), 262 (21), 228(82); HRMS Calc'd for C₁₈ H₁₄ ClNO₂ S: 343.0434. Found: 343.0434.

Anal. Calc'd for C₁₈ H₁₄ ClNO₂ S: C, 62.88; H, 4.10; N, 4.07.

Found: C, 62.66; H, 4.36; N, 4.09.

EXAMPLE 4 ##STR19## Step 1 Preparation of 1-bromo-2-4-(methylthio)phenyl!benzene

Following the general procedure outlined in Synthetic Scheme IV, 33 g(140 mmol) of 1,2-dibromobenzene was reacted with 12 g (70 mmol) of4-methylthiophenylboronic acid (Example 1, Step 2). Purification bysilica gel chromatography with hexane gave 17.2 g (89%) of 1-bromo-2-4-(methylthio)phenyl!benzene as a colorless oil: NMR (CDCl₃) δ 2.53 (s,3H), 7.16-7.23 (m, 1H), 7.28-7.39 (m, 6H), 7.66 (d, J=8 Hz, 1H).

Step 2 Preparation of 1-bromo-2- 4-(methylsulfonyl)phenyl!benzene

Following the synthetic procedure outlined in Step 4 of Example 1, 17.1g (61.3 mmol) of 1-bromo-2- 4-(methylthio)phenyl!benzene (Step 1) wasoxidized to its corresponding sulfone. Purification by silica gelchromatography (Waters Prep-500A) with ethyl acetate/hexane (3:7) gave16.2 g (85%) of 1-bromo-2- 4-(methylsulfonyl)phenyl!benzene as acolorless solid: mp 168.2°-169.5° C.; NMR (CDCl₃) δ 3.12 (s, 3H),7.23-7.33 (m, 2H), 7.40 (dt, J=1.5, 8 Hz, 1H), 7.61 (d, J=8 Hz, 2H),7.70 (dd, J=1.5, 8 Hz, 1H), 8.01 (d, J=9 Hz, 2H).

Step 3 Preparation of 3-fluoro-4-methoxyphenylboronic acid

Following the general procedure outlined in Synthetic Scheme I, 15 g (73mmol) of 4-bromo-2-fluoroanisole was converted to3-fluoro-4-methoxyphenylboronic acid: NMR (CDCl₃) δ 3.75 (s, 3H), 6.80(d, J=8 Hz, 1H), 7.36-7.48 (m, 2H).

Step 4 Preparation of 2-fluoro-1-methoxy-4- 2-4-(methylsulfonyl)phenyl!phenyl!benzene

Following the general procedure outlined in Synthetic Scheme VI, 5.0 g(16 mmol) of 1-bromo-2- 4-(methylsulfonyl)phenyl!benzene (Step 2) wasreacted with 4.1 g (24 mmol) of 3-fluoro-4-methoxyphenylboronic acid(Step 3). Purification by silica gel chromatography (Waters Prep-500A)with ethyl acetate/hexane (35:65) and subsequent recrystallization fromethyl acetate/hexane gave 4.82 g (88%) of 2-fluoro-1-methoxy-4- 2-4-(methylsulfonyl)phenyl!phenyl!benzene as a colorless solid:

mp 136.2°-136.6° C.; NMR (CDCl₃) δ 3.06 (s, 3H), 3.87 (s, 3H), 6.72-6.89(m, 3H), 7.31-7.51 (m, 6H), 7.81(d, J=9 Hz, 2H). MS (EI): m/e (relintensity) 356 (100), 262 (28) 246 (22); HRMS Calc'd for C₂₀ H₁₇ FO₃ S:356.0882. Found: 356.0881. Anal. Calc'd for C₂₀ H₁₇ FO₃ S: C, 67.40; H,4.81; F, 5.33. Found: C, 67.24; H, 4.83; F, 5.25.

EXAMPLE 5 ##STR20## Step 1 Preparation of 4-bromo-2-chloroanisole

Under nitrogen, 7.3 mL (77 mmol) of dimethylsulfate was added to astirred suspension of 10 g (48 mmol) of 4-bromo-2-chlorophenol and 5.4 g(38 mmol) of powered K₂ CO₃ in 75 mL of fresh acetone. After 2 hours atreflux, the reaction was cooled to ambient temperature, filtered, andconcentrated in vacuo. The residue was dissolved in ethyl acetate; theresulting solution was washed with water and dried over MgSO₄.Concentration in vacuo gave 10.2 g (96%) of 4-bromo-2-chloroanisole as acolorless solid: mp 68.5°-70.5° C.; NHR (CDCl₃) δ 3.88 (s, 3H), 6.80 (d,J=9 Hz, 1H), 7.33 (dd, J=2, 9 Hz, 1H), 7.50 (d, J=2 Hz, 1H).

Step 2 Preparation of 3-chloro-4-methoxyphenylboronic acid

Following the general procedure outlined in Synthetic Scheme I, 10.2 g(46.2 mmol) of 4-bromo-2-chloroanisole (Step 1) was converted to3-chloro-4-methoxyphenylboronic acid: NMR (CDCl₃) δ 3.83 (s, 3H), 6.57(s, 2H), 6.83 (d, J=8 Hz, 1H), 7.64 (dd, J=1.5, 8 Hz, 1H), 7.77 (d,J=1.5 Hz, 1H).

Step 3 Preparation of 2-chloro-1-methoxy-4- 2-4-(methylsulfonyl)phenyl!phenyl!benzene

Following the general procedure outlined in Synthetic Scheme VI, 4.0 g(13 mmol) of 1-bromo-2- 4-(methylsulfonyl)phenyl!benzene (Example 4,Step 2) was reacted with 2.86 g (15.4 mmol) of3-chloro-4-methoxyphenylboronic acid (Step 2). Purification by silicagel chromatography (Waters PrepLC 500A) with ethyl acetate/hexane(35:65) and subsequent recrystallization from ethyl acetate/hexane gave3.31 g (69%) of 2-chloro-1-methoxy-4- 2-4-(methylsulfonyl)phenyl!phenyl!benzene as a colorless solid: mp161.5°-162.3° C.; NMR (CDCl₃) δ 3.05 (s, 3H), 3.88 (s, 3H), 6.75 (d, J=9Hz, 1H), 6.87 (dd, J=1.5, 9 Hz, 1H), 7.17 (d, J=2 Hz, 1H), 7.34(d, J=9Hz, 2H), 7.37-7.51 (m, 4H), 7.82 (d, J=8 Hz, 2H). MS (EI): m/e (relintensity) 372 (100), 243 (24); HRMS Calc'd for C₂₀ H₁₇ ClO₃ S:372.0587. Found: 372.0557. Anal. Calc'd for C₂₀ H₁₇ ClO₃ S: C, 64.43; H,4.60; Cl, 9.51. Found: C, 64.17; H, 4.56; Cl, 9.63.

EXAMPLE 6 ##STR21## Step 1 Preparation of 4-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide

Under nitrogen, 5.8 mL (9.2 mmol) of propylmagnesium chloride (1.6M inEt₂ O) was added to a stirred solution of 3.0 g (8.4 mmol) of2-fluoro-1-methoxy-4- 2- 4-(methylsulfonyl)phenyl!phenyl!benzene (thetitle compound of Example 4, Step 4) in 9.6 mL of anhydroustetrahydrofuran at 0° C. The resulting solution was warmed to ambienttemperature and stirred for 30 minutes. The reaction was cooled to 0° C.prior to the addition of 12.6 mL (12.6 mmol) of triethylborane (1.0M inTHF). The reaction was warmed to ambient temperature and stirred for 90minutes prior to stirring at reflux for 40 hours. The reaction wascooled to 0° C. and treated with 6.4 g (78mmol) of sodium acetate, 3.8 g(34 mmol) of hydroxylamine-O-sulfonic acid, and 11 mL of water; stirringwas continued as the reaction slowly warmed to ambient temperature. Thereaction mixture was diluted with water and extracted three times withethyl acetate. The combined ethyl acetate extractions were washed withbrine and dried over MgSO₄. Purification by silica gel chromatography(Waters LC-2000) with ethyl acetate/hexane (3:7) and subsequentrecrystallization from ethyl acetate/hexane gave 2.0 g (67%) of 4-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide as a colorlesssolid: mp 143.5°-145.5° C. (dec); NMR (CDCl₃) δ 3.96 (s, 3H), 4.90 (s,2H), 6.74-6.90 (m, 3H), 7.29 (d, J=9 Hz, 2H), 7.35-7.48 (m, 4H), 7.79(d, J=9 Hz, 2H). MS (FAB): m/e 364 (M+Li); HRMS Calc'd for C₁₉ H₁₆ FNO₃S: 357.0835.

Found: 357.0809. Anal. Calc'd for C₁₉ H₁₆ FNO₃ S (0.20 ethyl acetate &0.13 H₂ O) C, 63.04; H, 4.77; N, 3.71. Found: C, 63.03; H, 4.59; N,3.52.

EXAMPLE 7 ##STR22##

Following the general procedure outlined in Synthetic Scheme XI, 2.5 g(6.7 mmol) of 2-chloro-1-methoxy-4- 2-4-(methylsulfonyl)phenyl!phenyl!benzene (the title compound of Example5) was converted to its corresponding sulfonamide. Purification bysilica gel chromatography (Waters LC-2000) with ethyl acetate/hexane(3:7) and subsequent recrystallization from ethyl acetate/hexane gave1.31 g (52%) of 4- 2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamideas a colorless solid: mp 179.5°-180.2° C.; NMR (CDCl₃) δ 3.87 (s, 3H),4.76 (s, 2H), 6.75 (d, J=9 Hz, 1H), 6.86 (dd, J=2, 9 Hz, 1H), 7.20 (d,J=3 Hz, 1H), 7.29 (d, J=9 Hz, 2H), 7.35-7.47 (m, 4H), 7.79 (d, J=8 Hz,2H). MS (EI): m/e (rel intensity) 373 (100), 258 (17), 243 (29); HRMSCalc'd for C₁₉ H₁₆ ClNO₃ S: 373.0539. Found: 373.0587. Anal. Calc'd forC₁₉ H₁₆ ClNO₃ S: C, 61.04; H, 4.31; N, 3.75. Found: C, 60.76; H, 4.28;N, 3.48.

EXAMPLE 8 ##STR23##

Following the general procedure outlined in Synthetic Scheme VI, 2.3 g(7.4 mmol) of 1-bromo-2- 4-(methylsulfonyl)phenyl!benzene (Example 4,Step 2) was reacted with 1.7 g (11 mmol) of 4-chlorophenylboronic acid.Purification by silica gel chromatography (Waters Prep-500A) with ethylacetate/hexane (1:3) and subsequent recrystallization from ethylacetate/hexane gave 1.90 g (74%) of 1-(4-chlorophenyl)-2-4-(methylsulfonyl)phenyl!benzene as a colorless solid: mp 180.2°-180.6°C.; NMR (CDCl₃) δ 3.06 (s, 3H), 7.04 (d, J=8 Hz, 2H), 7.21 (d, J=8 Hz,2H), 7.33 (d, J=9 Hz, 2H), 7.38-7.51 (m, 4H), 7.81 (d, J=8 Hz, 2H). MS(EI): m/e (rel intensity) 342 (34), 228 (100); HRMS Calc'd for C₁₉ H₁₅ClO₂ S: 342.0481. Found: 342.0484. Anal. Calc'd for C₁₉ H₁₅ ClO₂ S: C,66.56; H, 4.41; Cl, 10.34. Found: C, 66.45; H, 4.48; Cl, 10.63.

EXAMPLE 9 ##STR24## Step 1 Preparation of4-(trifluoromethyl)phenylboronic acid

Following the general procedure outlined in Synthetic Scheme I, 8.9 g(39 mmol) of 4-bromobenzotrifluoride was converted to4-(trifluoromethyl)phenylboronic acid.

Step 2 Preparation of 1- 4-(trifluoromethyl)phenyl!-2-4-(methylsulfonyl)phenyl!benzene

Following the general procedure outlined in Synthetic Scheme VI, 4.0 g(13 mmol) of 1-bromo-2- 4-(methylsulfonyl)phenyl!benzene (Example 4,Step 2) was reacted with 3.8 g (20 mmol) of4-(trifluoromethyl)phenylboronic acid (Step 1). Purification by silicagel chromatography (Waters Prep-500A) with ethyl acetate/hexane (1:3)and subsequent recrystallization from ethyl acetate/hexane gave 3.80 g(77%) of 1- 4-(trifluoromethyl)phenyl!-2-4-(methylsulfonyl)phenyl!benzene as a colorless solid: mp 172.8°-173.5°C.; NMR (CDCl₃) δ 3.06 (s, 3H), 7.23 (d, J=8 Hz, 2H), 7.33 (d, J=9 Hz,2H), 7.41-7.46 (m, 2H), 7.48-7.54 (m, 4H), 7.81 (d, J=9 Hz, 2H). MS(ES): m/e 383 (M+Li); HRMS Calc'd for C₂₀ H₁₅ F₃ O₂ S: 376.0745. Found:376.0766.

Step 3 Preparation of 4- 2-4-(trifluoromethyl)phenyl!phenyl!benzenesulfonamide

Following the synthetic procedure outlined in Synthetic Scheme XI, 2.62g (6.96 mmol) of 1- 4-(trifluoromethyl)phenyl!-2-4-(methylsulfonyl)phenyl!benzene (Step 2) was converted to itscorresponding sulfonamide. Purification by silica gel chromatography(Water Prep-500A) with ethyl acetate/hexane (3:7) and subsequentrecrystallization from ethyl acetate/hexane gave 1.85 g (70%) of 4- 2-4-(trifluoromethyl)phenyl!phenyl!benzenesulfonamide as a colorlesssolid: mp 187.5°-187.8° C.; NMR (CDCl₃) δ 4.79 (s, 2H), 7.20-7.31 (m,4H), 7.38-7.54 (m, 6H), 7.80 (d, J=8 Hz, 2H). MS (EI): m/e (relintensity) 377 (14), 297 (25), 228 (100); HRMS Calc'd for C₁₉ H₁₄ F₃ NO₂S: 377.0697.

Found: 377.0737. Anal. Calc'd for C₁₉ H₁₄ F₃ NO₂ S: C, 60.47; H, 3.74;N, 3.71. Found: C, 60.43; H, 3.97; N, 3.48.

EXAMPLE 10 ##STR25## Step 1 Preparation of 2-chloro-1-fluoro-4- 2-4-(methylsulfonyl)phenyl!phenyl!benzene

Following the general procedure outlined in Synthetic Scheme VI, 6.43 g(20.6 mmol) of 1-bromo-2- 4-(methylsulfonyl)phenyl!benzene (Example 4,Step 2) was reacted with 5.37 g (30.9 mmol) of3-chloro-4-fluorophenylboronic acid. Purification by silica gelchromatography (Waters Prep-500A)with ethyl acetate/hexane (1:3) gave6.64 g (89%) of 2-chloro-1-fluoro-4- 2-4-(methylsulfonyl)phenyl!phenyl!benzene as a colorless solid: mp179.5°-181.1° C.; NMR (CDCl₃) δ 3.06 (s, 3H), 6.86-6.93 (m, 1H), 6.98(t, J=8 Hz, 1H), 7.19 (dd, J=2, 7 Hz, 1H), 7.33 (d, J=8 Hz, 2H),7.38-7.53 (m, 4H), 7.84 (d, J=9 Hz, 2H). MS (FAB): m/e 367 (M+Li); HRMSCalc'd for C₁₉ H₁₄ ClFO₂ S: 360.0387. Found: 360.0401. Anal. Calc'd forC₁₉ H₁₄ ClFO₂ S: C, 63.25; H, 3.91; F, 5.27. Found: C, 62.92; H, 4.02;F, 5.19.

EXAMPLE 11 ##STR26## Step 1 Preparation of1,2-difluoro-4-(4-fluorophenyl)-5- 4-(methylthio)phenyl!benzene

Under nitrogen, 3 g (2.6 mmol) of Pd(PPh₃)₄ was added to a stirredsolution of 5.0 g (18 mmol) of 1,2-dibromo-4,5-difluorobenzene(Aldrich), 4.2 g (25 mmol) of 4-methylthiophenylboronic acid (Example 1,Step 2), and 3.1 g (22 mmol) of 4-fluorophenylboronic acid in 100 mL oftoluene, 100 mL of ethanol, and 100 mL of 2M Na₂ CO₃. After vigorousstirring at reflux overnight, the solvent was removed in vacuo and theresidue dissolved in ethyl acetate. The resulting solution was washedwith water and dried over MgSO₄. Purification by silica gelchromatography gave 1,2-difluoro-4-(4-fluorophenyl)-5-4-(methylthio)phenyl!benzene as a semi-solid which was used withoutfurther purification.

Step 2 Preparation of 1,2-difluoro-4-(4-fluorophenyl)-5-4-(methylsulfonyl)phenyl!benzene

To a stirred solution of 6.34 g (ca. 18 mmol) of the crude1,2-difluoro-4-(4-fluorophenyl)-5- 4-(methylthio)phenyl!benzene (Step 1)in 125 mL of methylene chloride at 0° C. was slowly added 14.6 g (54mmol) of 3-chloroperoxybenzoic acid (ca 64%); after stirring for 90minutes, the reaction was diluted with additional methylene chloride,washed with 3 times with 5% NaOH, and dried over MgSO₄. Purification bysilica gel chromatography (Waters Prep-500A) with ethyl acetate/hexane(1:3) and subsequent recrystallization from ethyl acetate/hexane gave2.81 g (43%) of 1,2-difluoro-4-(4-fluorophenyl)-5-4-(methylsulfonyl)phenyl!benzene as a colorless solid: mp 172.8°-173.5°C.; NMR (CDCl₃) δ 3.05 (s, 3H), 6.94 (t, J=8 Hz, 2H), 6.98-7.06 (m, 2H),7.21-7.31 (m, 4H), 7.81 (d, J=8 Hz, 2H). MS (FAB): m/e 369 (M+Li); HRMSCalc'd for C₁₉ H₁₃ F₃ O₂ S: 362.0588. Found: 362.0586. Anal. Calc'd forC₁₉ H₁₃ F₃ O₂ S: C, 62.98; H, 3.62; F, 15.73. Found: C, 62.96; H, 3.70;F, 15.76.

EXAMPLE 12 ##STR27##

Following the general procedure outlined in Synthetic Scheme XI, 5.0 g(14 mmol) of 2-chloro-1-fluoro-4- 2-4-(methylsulfonyl)phenyl!phenyl!benzene (the title compound of Example10) was converted to its corresponding sulfonamide. Purification bysilica gel chromatography (Waters Prep-500A) with ethyl acetate/hexane(28:72) and subsequent recrystallization from ethyl acetate/hexane gave1.47 g (29%) of 4- 2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamideas a colorless solid: mp 192.5°-193.2° C.; NMR (CDCl₃) δ 6.36 (s, 2H),6.68-6.76 (m, 1H), 6.81 (t, J=9 Hz, 1H), 7.06 (d, J=8 Hz, 2H), 7.17-7.32(m, 5H), 7.63 (d, J=8, 2H). MS (FAB): m/e 368 (M+Li); HRMS Calc'd forC₁₈ H₁₃ ClFNO₂ S: 361.0340.

Found: 361.0338. Anal. Calc'd for C₁₈ H₁₃ ClFNO₂ S: C, 59.75; H, 3.62;N, 3.87. Found: C, 59.80; H, 3.91; N, 4.05.

EXAMPLE 13 ##STR28##

Following the general procedure outlined in Synthetic Scheme XI, 2.65 g(7.32 mmol) of 1,2-difluoro-4-(4-fluorophenyl)-5-4-(methylsulfonyl)phenyl!benzene (the title compound of Example 11) wasconverted to its corresponding sulfonamide. Purification by silica gelchromatography (Waters LC-2000) with ethyl acetate/hexane (1:3) andsubsequent recrystallization from ethyl acetate/hexane gave 1.37 g (52%)of 4- 3,4-difluoro-6-(4-fluorophenyl)phenyl!benzenesulfonamide as acolorless solid: mp 190.2°-191.5° C.; NMR (CDCl₃) δ 4.77 (s, 2H), 6.94(t, J=8 Hz, 2H), 6.98-7.06 (m, 2H), 7.17-7.28 (m, 4H), 7.79 (d, J=8 Hz,2H). MS (FAB): m/e 370(M+Li); HRMS Calc'd for C₁₈ H₁₂ F₃ NO₂ S:363.0541. Found: 363.0576.

Anal. Calc'd for C₁₈ H₁₂ F₃ NO₂ S: C, 59.50; H, 3.33; N, 3.85. Found: C,59.52; H, 3.57; N, 3.68.

EXAMPLE 14 ##STR29## Step 1 Preparation of1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2- 4-(methylthio)phenyl!benzene

Following the general procedure outlined in Synthetic Scheme VII, 4.1 g(15 mmol) of 1,2-dibromo-4,5-difluorobenzene, 3.0 g (18 mmol) of4-methylthiophenylboronic acid (Example 1, Step 2) and 2.9 g (16.5 mmol)of 3-chloro-4-fluorophenylboronic acid were reacted. Purification bysilica gel chromatography gave 3.5 g of1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2- 4-(methylthio)phenyl!benzeneas a semi-solid which was used without further purification.

Step 2 Preparation of 1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene

Following the synthetic procedure outlined in Step 2 of Example 11, 3.50g (ca. 15 mmol) of crude 1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2-4-(methylthio)phenyl!benzene (Step 1) was oxidized to its correspondingsulfonamide. Purification by silica gel chromatography (WatersPrep-500A) with ethyl acetate/hexane (1:3) and subsequentrecrystallization from ethyl acetate/hexane gave 1.66 g (28%) of1-(3-Chloro-4-fluorophenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene as a colorless solid: mp 172.2°-172.5°C.; NMR (CDCl₃) δ 3.05 (s, 3H), 6.82-6.89 (m, 1H), 6.99 (t, J=9 Hz, 1H),7.14 (dd, J=2, 8 Hz, 1H), 7.20-7.32 (m, 4H), 7.84(d, J=8 Hz, 2H); MS(EI): m/e (rel intensity) 396-(22), 317 (12), 282-(100), 262 (25),243-(10); HRMS Calc'd for C₁₉ H₁₂ Cl F₃ O₂ S: 396.0199.

Found: 396.0203. Anal. Calc'd for C₁₉ H₁₂ ClF₃ O₂ S: C, 57.51; H, 3.05;F, 14.36. Found: C, 57.31; H, 2.99; F, 14.48.

EXAMPLE 15 ##STR30## Step 1 Preparation of1,2,3,4-tetrafluoro-5-(4-fluorophenyl)-6- 4-(methylthio)phenyl!benzene

Under nitrogen, 1 g of Pd(PPh₃)₄ was added to a stirred solution of 4.85g (15.8 mmol) of 1,2-dibromo-3,4,5,6-tetrafluorobenzene (Aldrich), 2.65g (18.9 mmol) of 4-fluorophenylboronic acid, and 3.17 g (18.9 mmol) of4-methylthiophenylboronic acid (Example 1, Step 2) in 80 mL of toluene,50 mL of ethanol, and 35 mL of 2M Na₂ CO₃. After vigorous stirring atreflux overnight, the solvent was removed in vacuo. The residue wasdissolved in ethyl acetate, washed water, and dried over Na₂ SO₄.Concentration in vacuo gave 7.3 g of1,2,3,4-tetrafluoro-5-(4-fluorophenyl)-6- 4-(methylthio)phenyl!benzeneas a yellow oil which was used without further purification.

Step 2 Preparation of 1,2,3,4-tetrafluoro-5-(4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!benzene

To a stirred solution of 7.3 g of crude1,2,3,4-tetrafluoro-5-(4-fluorophenyl)-6- 4-(methylthio)phenyl!benzene(Step 1) in 40 mL of methylene chloride was slowly added 15 g (43.5mmol) of 3-chloroperoxybenzoic acid (ca 55%) at -10° C. Purification bysilica gel chromatography (MPLC) with ethyl acetate/hexane (1:5)followed by reversed phase chromatography (Waters DeltaPrep-3000) withacetonitrile/water/TFA (48:52:0.05) gave 1.2 g (19% overall for bothsteps) of 1,2,3,4-tetrafluoro-5-(4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!benzene as a colorless solid:

mp 134.0°-135.0° C.; NMR (CDCl₃) δ 3.05 (s, 3H), 6.91-7.03 (m, 4H),7.26(d, J=8.5 Hz, 2H), 7.84(d, J=8.5 Hz, 2H). MS (FAB): m/e 405 (M+Li);HRMS Calc'd for C₁₉ H₁₁ F₅ O₂ S: 398.0400, found: 398.0393.

Step 3 Preparation of 4-2,3,4,5-tetrafluoro-6-(4-fluorophenyl)phenyl!benzenesulfonamide

Following the general procedure outlined in Synthetic Scheme XI, 1.1 g(2.76 mmol) of 1,2,3,4-tetrafluoro-5 (4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!benzene (Step 2) was converted to itscorresponding sulfonamide. Purification by silica gel chromatography(MPLC) with ethyl acetate/hexane (1:5) gave 80 mg (7%) 4-2,3,4,5-tetrafluoro-6-(4-fluorophenyl)phenyl!benzenesulfonamide as acolorless solid: mp 202.0°-203.0° C.; NMR (CDCl₃) δ 4.78 (br s, 2H),6.92-7.04 (m, 4H), 7.21(d, J=8.5 Hz, 2H), 7.82(d, J=8.5 Hz, 2H). MS(FAB): m/e 406 (M+Li). Anal. Calc'd for C₁₈ H₁₀ F₅ NO₂ S. (0.16 H₂ O):C, 53.76; H, 2.59; N, 3.48. Found: C, 53.73; H, 2.40; N, 3.44.

EXAMPLE 16 ##STR31##

Following the general procedure outlined in Synthetic Scheme XI, 2.00 g(5.04 mmol) of 1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene (the title compound of Example 14) wasconverted to its corresponding sulfonamide. Purification by reversephase chromatography (Waters DeltaPrep-3000) with acetonitrile/water/TFA(48:52:0.05) and subsequent recrystallization from ethyl acetate/hexanegave 500 mg (25%) of 4-2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide as acolorless solid: mp 162.5°-162.8° C.; NMR (CDCl₃) δ 4.80 (s, 2H),6.81-6.88 (m, 1H), 6.99 (t, J=9 Hz, 1H), 7.15-7.28 (m, 5H), 7.83(d, J=8Hz, 2H). MS (FAB): m/e 404 (M+Li); HRMS Calc'd for C₁₈ H₁₁ ClF₃ NO₂ S:397.0151. Found: 397.0152. Anal. Calc'd for C₁₈ H₁₁ ClF₃ NO₂ S: C,54.35; H, 2.79; N, 3.52. Found: C, 54.57; H, 3.00; N, 3.42.

EXAMPLE 17 ##STR32## Step 1 5-(4-fluorophenyl)-6-4-(methylthio)phenyl!-1,3-benzodioxole

Under nitrogen, 1 g of Pd(PPh₃)₄ was added to a stirred solution of 4 g(14.3 mmol) of 5,6-dibromo-1,3-benzodioxole (Lancaster), 2.4 g (17.2mmol) of 4-fluorophenyl boronic acid, and 2.87 g (17.2 mmol) of4-methylthiophenylboronic acid (Example 1, Step 2) in 70 mL of toluene,40 mL of ethanol, and 30 mL of 2M Na₂ CO₃. After vigorous stirring atreflux overnight, the solvent was removed in vacuo. The residue wasdissolved in ethyl acetate, washed with water, and dried over Na₂ SO₄.Concentration in vacuo gave 6.9 g of 5-(4-fluorophenyl)-6-4-(methylthio)phenyl!-1,3-benzodioxole as a semi-solid which was usedwithout further purification.

Step 2 Preparation of 5-(4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole

To a stirred solution of 6.9 g of 5-(4-fluorophenyl)-6-4-(methylthio)phenyl!-1,3-benzodioxole (Step 1) in 30 mL of methylenechloride was slowly added 12 g (38.2 mmol) of 3-chloroperoxybenzoic acid(ca. 55%) at -10° C. Purification by silica gel chromatography (MPLC)with ethyl acetate/hexane (1:4) followed by reversed phasechromatography (Waters DeltaPrep-3000) with acetonitrile/water/TFA(45:55:0.05) gave 200 mg (4% overall for both steps) of5-(4-fluorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole as acolorless solid: mp 173.0°-174.0° C.; NMR (CDCl₃) δ 3.04 (s, 3H), 6.06(s, 2H), 6.86-6.92 (m, 4H), 6.96-7.03 (m, 2H), 7.23-7.27 (m, 2H),7.76(d, J=8.5 Hz, 2H). MS (FAB): m/e 377 (M+Li); HRMS Calc'd for C₂₀ H₁₅FO₄ S: 370.0675, found: 370.0680. Anal. Calc'd for C₂₀ H₁₅ FO₄ S (0.25H₂ O): C, 64.08; H, 4.17. Found: C, 64.08; H, 4.15.

EXAMPLE 18 ##STR33## Step 1 Preparation of 1-bromo-4,5-difluoro-2-4-(methylthio)phenyl!benzene

Following the general procedure outlined in Synthetic Scheme IV, 40 g(147 mmol) of 1,2-dibromo-4,5-difluorobenzene was reacted with 12.3 g(73 mmol) of 4-methylthiophenylboronic acid (Example 1, Step 2).Purification by silica gel chromatography with hexane gave 40.3 g of1-bromo-4,5-difluoro-2- 4-(methylthio)phenyl!benzene as a yellow oilwhich was used without further purification.

Step 2 Preparation of 1-bromo-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene

Following the synthetic procedure outlined in Step 4 of Example 1, 40.3g (ca. 73 mmol) of 1-bromo-4,5-difluoro-2- 4-(methylthio)phenyl!benzene(Step 1) was oxidized to its corresponding sulfone. Purification bysilica gel chromatography (Waters Prep-500A) with ethyl acetate/hexane(1,3) gave 17.4 g (68%) of 1-bromo-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene as a colorless solid: mp 158.5°-159.5°C.; NMR (CDCl₃) δ 3.12 (s, 3H), 7.13-7.21 (m, 1H), 7.50-7.60 (m, 3H),8.02(d, J=9 Hz, 2H).

Step 3 Preparation of 1-(3-chloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene

Following the general procedure outlined in Synthetic Scheme VI, 4.4 g(13 mmol) of 1-bromo-4,5-difluoro-2- 4-(methylsulfonyl)phenyl!benzene(Step 2) was reacted with 3.1 g (17 mmol) of 3-chloro-4-methoxyphenylboronic acid (Example 5, Step 2). Purification by silica gelchromatography (Waters Prep-500A) with ethyl acetate/hexane (3:7) andsubsequent recrystallization from ethyl acetate/hexane gave 4.47 g (95%)of 1-(3-chloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene as a colorless solid: mp 147.5°-148.5°C.; NMR (CDCl₃) δ 3.05 (s, 3H), 3.88 (s, 3H), 6.75(d, J=9 Hz, 1H), 6.83(dd, J=2, 9 Hz, 1H), 7.10(d, J=2 Hz, 1H), 7.17-7.32 (m, 4H), 7.83(d, J=9Hz, 2H). MS (EI): m/e (rel intensity) 408 (33), 314 (15), 294 (52), 279(63), 251 (100). Anal. Calc'd for C₂₀ H₁₅ ClF₂ O₃ S.(0.27 ethylacetate): C, 58.53; H, 3.99; F, 8.79. Found: C, 58.75; H, 3.71; F, 8.52.

EXAMPLE 19 ##STR34##

Following the general procedure outlined in Synthetic Scheme VI, 3.0 g(8.6 mmol) of 1-bromo-4,5-difluoro-2- 4-(methylsulfonyl)phenyl!benzene(Example 18, Step 2) was reacted with 1.9 g (11 mmol) of3-fluoro-4-methoxyphenylboronic acid (Example 4, Step 3). Purificationby silica gel chromatography (Waters Prep500A) with ethyl acetate/hexane(1:3) and subsequent recrystallization from ethyl acetate/hexane gave3.19 g (94%) of 1,2-difluoro-4-(3-fluoro-4-methoxyphenyl)- benzene as achloroethylsulfonyl)phenyl!benzene as a colorless solid: mp159.2°-159.7° C.; NMR (CDCl₃) δ 3.05 (s, 3H), 3.87 (s, 3H), 6.63-6.85(m, 3H), 7.16-7.32 (m, 4H), 7.82(d, J=8 Hz, 2H). MS (EI): m/e (relintensity) 392 (49), 313 (15), 298 (48), 269 (100), 249 (79). Anal.Calc'd for C₂₀ H₁₅ F₃ O₃ S (0.26 ethyl acetate): C, 60.85; H, 4.15; F,13.71. Found: C, 61.33; H, 3.90; F, 13.40.

EXAMPLE 20 ##STR35##

Following the general procedure outlined in Synthetic Scheme XI, 4.00 g(9.78 mmol) of 1-(3-chloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene (the title compound of Example 18) wasconverted to its corresponding sulfonamide. Purification by silica gelchromatography (HPLC) with ethyl acetate/hexane (1:3) and subsequentrecrystallization from ethyl acetate/hexane gave 0.86 g (21%) of 4-2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide as acolorless solid: mp 70° C. (dec); NHR (CDCl₃) δ 3.87 (s, 3H), 4.84 (s,2H), 6.75(d, J=9 Hz, 1H), 6.82 (dd, J=2, 9 Hz, 1H), 7.14(d, J=2 Hz, 1H),7.16-7.28 (m, 4H), 7.81 (d, J=8, 2H). MS (EI): m/e (rel intensity) 409(22), 294 (15), 279 (28), 251 (100), 231 (20). Anal. Calc'd for C₁₉ H₁₄ClF₂ NO₃ S: C, 55.68; H, 3.44; N, 3.42. Found: C, 55.42; H, 3.48; N,3.33.

EXAMPLE 21 ##STR36##

Following the general procedure outlined in Synthetic Scheme XI; 2.50 g(6.38 mmol) of 1,2-difluoro-4-(3-fluoro-4-methoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene (the title compound of Example 19) wasconverted to its corresponding sulfonamide. Purification by silica gelchromatography (MPLC) with ethyl acetate/hexane (1:3) and subsequentrecrystallization from ethyl acetate/hexane gave 0.82 g (33%) of 4-4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide as acolorless solid: mp 132.2°-132.8° C.; NMR (CDCl₃) δ 3.87 (s, 3H), 4.85(s, 2H), 6.71-6.85 (m, 3H), 7.15-7.27 (m, 4H), 7.81(d, J=9 Hz, 2H). MS(EI): m/e (rel intensity) 393(32), 298 (21), 282 (25), 269 (100), 249(46). Anal. Calc'd for C₁₉ H₁₄ F₃ NO₃ S: C, 58.01; H, 3.59; N, 3.56.Found: C, 57.75; H, 3.48; N, 3.48.

EXAMPLE 22 ##STR37## Step 1 Preparation of5-bromo-6-(4-fluorophenyl)-1,3-benzodioxole

Under nitrogen, 1.1 g of Pd(PPh₃)₄ was added to a stirred solution of10.4 g (37.2 mmol) of 5,6-dibromo-1,3-benzodioxole and 2.6 g (18.6 mmol)of 4-fluorophenylboronic acid in 100 mL of toluene, 60 mL of ethanol,and 40 mL of M Na₂ CO₃. After vigorous stirring at reflux overnight, thesolvent was removed in vacuo. The residue was dissolved in ethylacetate, washed with water, and dried over Na₂ SO₄. Purification bysilica gel chromatography (Waters Prep-500A) with hexane as the eluentgave 3.9 g (71%) of 5-bromo-6 (4-fluorophenyl)-1,3-benzodioxole as acolorless solid: mp 86.0°-87.5° C.; NMR (CDCl₃) δ 6.02 (s, H), 6.77 (s,1H), 7.04-7.13 (m, 3H), 7.28-7.35 (m, 2H).

Step 2 Preparation of 6 (4-fluorophenyl)-1,3-benzodioxol-5-yl!boronicacid

Under nitrogen, 6.3 mL (15.8 mmol) of n-BuLi (2.5M in hexanes) was addedto a stirred solution of 3.9 g (13.2 mmol) of5-bromo-6-(4-fluorophenyl)-1,3-benzodioxole (Step 1) in 30 mL ofanhydrous THF at -78° C. After 30 minutes, 4.5 mL (39.4 mmol) oftrimethylborate was added. The reaction was warmed to ambienttemperature and stirred for 3 hours prior to the addition of 60 mL of 5%NaOH. The reaction was stirred for an additional 60 minutes, the THFremoved in vacuo, and the pH adjusted to ca. 4. The residue wasdissolved in ethyl acetate; the resulting solution was dried over Na₂S04 and concentrated in vacuo to give 1.7 g (50%) of 6(4-fluorophenyl)-1,3-benzodioxol-5-yl! boronic acid as a pale yellowsolid: NMR (CDCl₃) δ 4.00 (br s, 2H), 6.06 (s, 2H), 6.75 (s, 1H),7.08-7.17 (m, 2H), 7.26 (s, 1H), 7.31-7.39 (m, 2H).

Step 3 Preparation of 4- 6(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide

Under nitrogen, 500 mg of Pd(PPh₃)₄ was added to a stirred solution of1.55 g (6.0 mmol) of 6-(4-fluorophenyl)-1,3-benzodioxol-5-yl!boronicacid (Step 2) and 1.09 g (4.62 mmol)of 4-bromobenzenesulfonamide(Lancaster) in 30 mL of toluene, 20 mL of ethanol, and 15 mL of 2M Na₂CO₃. After vigorous stirring at reflux for 6hours, the solvent wasremoved in vacuo and the residue dissolved in ethyl acetate. Theresulting solution was washed with water and dried over Na₂ SO₄.Purification by silica gel chromatography (MPLC)with ethylacetate/hexane (3:7) gave 1.3 g (76%) of 4-6-(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide as acolorless solid: mp 191.0°-192.5° C.; NMR (CDCl₃) δ 4.80 (s, 2H), 6.06(s, 2H), 6.83-6.92 (m, 4H), 6.97-7.06 (m, 2H), 7.20(d, J=8.5 Hz, 2H),7.74(d, J=8.5 Hz, 2H). MS (FAB): m/e 372 (H+H). Anal. Calc'd for C₁₉ H₁₄FNO₄ S: C, 61.45; H, 3.80; N, 3.77. Found: C, 61.48; H, 3.92; N, 3.68.

EXAMPLE 23 ##STR38##

Following the general procedure outlined in Synthetic Scheme VI, 2.56 g(7.37 mmol) of 1-bromo-4,5-difluoro-2- (4-methylsulfonyl)phenyl!benzene(Example 18; Step 2) was reacted with 1.35 g (9.93 mmol) of4-methylphenylboronic acid. Purification by silica gel chromatography(MPLC) with ethyl acetate/hexane (3:7) gave 2.55 g (97%) of1,2-difluoro-4-(4-methylphenyl)-5- 4-(methylsulfonyl)phenyl!benzene as acolorless solid: mp 147.0°-148.0° C.; NMR (CDCl₃) δ 2.32 (s, 3H), 3.05(s, 3H), 6.92(d, J=8 Hz, 2H), 7.03(d, J=8 Hz, 2H), 7.17-7.32(m, 4H),7.79(d, J=8 Hz, 2H). MS (FAB): m/e 365(M+Li). Anal. Calc'd for C₂₀ H₁₆F₂ O₂ S: C, 67.03; H, 4.50. Found: C, 67.18; H, 4.48.

EXAMPLE 24 ##STR39## Step 1 Preparation of (1,3-benzodioxol-5-yl)boronicacid

Following the synthetic procedure outlined in Step 2 of Example 1, 15.2g (75.6 mole) of 5-bromo-1,3-benzodioxole (Aldrich) was converted to(1,3-benzodioxol-5-yl)boronic acid as a colorless solid: NMR (CDCl₃) δ5.98 (s, 2H), 6.88 (t, J=8 Hz, 1H), 7.26-7.41 (m, 2H), 7.80 (br s, 2H).

Step 2 Preparation of 5- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-1,3-benzodioxole

Following the general procedure outlined in Synthetic Scheme I, 2.24 g(6.45 mmol) of 1-bromo-4,5-difluoro-2- 4-(methylsulfonyl)phenyl!benzene(Example 18, Step 2) was reacted with 1.39 g (8.38 mmol) of(1,3-benzodioxol-5-yl)boronic acid (Step 1). Purification by silica gelchromatography (MPLC) with ethyl acetate/hexane (1:4) gave 2.47 g (99%)of 5- 4,5-difluoro-2- 4-(methylsulfonyl)phenyl!phenyl!-1,3-benzodioxoleas a colorless solid: mp 110.0°-111.0° C.; NMR (CDCl₃) δ 3.05 (s, 3H),5.95 (s, 2H), 6.47-6.52 (m, 2H), 6.67(d, J=8.5 Hz, 1H), 7.16-7.24 (m,2H), 7.32(d, J=8.5 Hz, 2H), 7.82 (d, J=8.5 Hz, 2H). MS (FAB): m/e 395(M+Li). Anal. Calc'd for C₂₀ H₁₄ F₂ O₄ S: C, 61.85; H, 3.63; Found: C,1.92; H, 3.66.

EXAMPLE 25 ##STR40##

Following the general procedure outlined in Synthetic Scheme XI, 2.43 g(6.78 mmol) of 1,2-difluoro-4-(4-methylphenyl)-5-4-(methylsulfonyl)phenyl!benzene (the title compound of Example 23) wasconverted to its corresponding sulfonamide. Purification by silica gelchromatography (MPLC) with ethyl acetate/hexane (1:5) gave 1.90 g (78%)of 4- 4,5-difluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide as acolorless solid: mp 103.0°-104.0° C.; NMR (CDCl₃) δ 2.32 (s, 3H), 4.81(s, 2H), 6.93(d, J=8 Hz, 2H), 7.04(d, J=8 Hz, 2H) 7.16-7.29 (m, 4H),7.78(d, J=8.5 Hz, 2H). MS (EI): m/e 359 (26), 279 (33), 278 (41), 264(100), 251 (36), 119 (62 , 80(70), 64 (56). Anal. Calc'd for C₁₉ H₁₅ F₂NO₂ S: C, 63.50; H, 4.21; N, 3.90. Found: C, 63.55; H, 4.24; N, 3.80.

EXAMPLE 26 ##STR41##

Following the general procedure outlined in Synthetic Scheme XI, 2.34 g(6.02 mmol) of 5- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-1,3-benzodioxole (the title compound ofExample 24) was converted to its corresponding sulfonamide. Purificationby silica gel chromatography (MPLC) with ethyl acetate/hexane (3:7) gave1.84 g (78%) of 4-2-(1,3-benzodioxol-5-yl)-4,5-difluorophenyl!benzenesulfonamide as acolorless solid: mp 142.0°-143.0° C.; NMR (CDCl₃) δ 4.83 (s, 2H), 5.95(s, 2H), 6.49-6.54 (m, 2H), 6.69(d, J=8 Hz, 1H), 7.15-7.30 (m, H),7.81(d, J=8 Hz, 2H). MS (EI): m/e 389 (18), 308 (14), 251 (100), 231(43). Anal. Calc'd for C₁₉ H₁₃ F₂ NO₄ S.(0.19 H₂ O): C, 58.09; H, 3.43;N, 3.57. Found: C, 58.11; H, 3.51; N, 3.48.

EXAMPLE 27 ##STR42## Step 1 Preparation of3-chloro-4-methylphenylboronic acid

Following the general procedure outlined in Synthetic Scheme I, 11.1 g(54 mmol) of 4-bromo-2chlorotoluene was converted to3-chloro-4-methylphenylboronic acid as a colorless solid: NMR (CDCl₃) δ2.47 (s, 3H), 7.37(d, J=8 Hz, 1H), 7.98 (d, J=8 Hz, 1H), 8.08 (s, 1H).

Step 2 Preparation of 1-(3-chloro-4-methylphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene

Following the general procedure outlined in Synthetic Scheme VI, 2.49 g(7.17 mmol) of 1-bromo-4,5-difluoro-2- 4-(methylsulfonyl)phenyl!benzene(Example 18, Step 2) was reacted with 1.59 g (9.33 mmol) of3-chloro-4-methylphenylboronic acid (Step 1). Purification by silica gelchromatography (HPLC) with ethyl acetate/hexane (1:5) gave 2.65 g (94%)of 1-(3-chloro-4-methylphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene as a colorless solid: mp 138.0°-139.0°C.; NMR (CDCl₃) δ 2.34 (s, 3H), 3.05 (s, 3H), 6.75 (dd, J=2, 8 Hz, 1H),7.03-7.10 (m, 2H), 7.18-7.26 (m, 2H), 7.29 (d, J=8 Hz, 2H), 7.83 (d, J=8Hz, 2H). MS (FAB): m/e 399 (M+Li). Anal. Calc'd for C₂₀ H₁₅ ClF₂ O₂ S:C, 61.15; H, 3.85. Found: C, 61.12; H, 3.82.

EXAMPLE 28 ##STR43## Step 1 Preparation of4-bromo-2-chloro-N,N-dimethylaniline

Under nitrogen, 11.6 mL (186 mmol) of iodomethane was added to a stirredsolution of 12.8 g (62 mmol) of 4-bromo-2-chloroaniline and 42.8 g (310mmol) of powdered K₂ CO₃ in 200 mL of DMF. Purification by silica gelchromatography (Waters Prep-500A)with ethyl acetate/hexane (5:95) gave11.3 g (78%) of 4-bromo-2-chloro-N,N-dimethylaniline as a colorlessliquid: NMR (CDCl₃) δ 2.79 (s, 6H), 6.92(d, J=9 Hz, 1H), 7.25-7.34 (m,1H), 7.49 (d, J=2 Hz, 1H).

Step 2 Preparation of 3-chloro-4-(N,N-dimethylamino)phenylboronic acid

Following the general procedure outlined in Synthetic Scheme I, 11.3 g(48.2 mmol) of 4-bromo-2-chloro-N,N-dimethylaniline (Step 1) wasconverted to 3-chloro-4-(N,N-dimethylamino)phenylboronic acid as acolorless solid: NMR (CDCl₃) δ 2.93 (s, 6H), 7.12 (d, J=8 Hz, 1H), 8.01(d, J=8 Hz, 1H), 8.12 (s, 1H).

Step 3 Preparation of 2-chloro-4- 4,5-difluoro-2- 4-(methylsulfonyl)phenyl! phenyl!-N,N-dimethylbenzenamine

Following the general procedure outlined in Synthetic Scheme VI, 2.25 g(6.48 mmol) of 1-bromo-4,5-difluoro-2- 4-(methylsulfonyl)phenyl!benzene(Example 18, Step 2) was reacted with 1.68 g (8.42 mmol) of3-chloro-4-(N,N-dimethylamino)phenylboronic acid (Step 2). Purificationby silica gel chromatography (MPLC) with ethyl acetate/hexane (3:7) gave2.65 g (97%) of 2-chloro-4- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-N,N-dimethylbenzenamine as a colorlesssolid: mp 129.0°-130.0° C.; NMR (CDCl₃) β 2.81 (s, 6H), 3.05 (s, 3H),6.76-6.91 (m, 2H), 7.08(d, J=2 Hz, 1H), 7.17-7.26 (m, 2H), 7.31 (d,J=8.5 Hz, 2H), 7.83(d, J=8.5 Hz, 2H). MS (FAB): m/e 428 (M+Li). Anal.Calc'd for C₂₁ H₁₈ ClF₂ NO₂ S: C, 59.79; H, 4.30; N, 3.32. Found: C,59.40; H, 4.29; N, 3.24.

EXAMPLE 29 ##STR44##

Following the general procedure outlined in Synthetic Scheme XI, 2.54 g(6.47 mmol) of 1-(3-chloro-4-methylphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene (the title compound of Example 27) wasconverted to its corresponding sulfonamide. Purification by silica gelchromatography (MPLC) with ethyl acetate/hexane (1:5) gave 1.80 g (71%)of 4- 2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamideas a colorless solid: mp 139.0°-140.0° C.; NMR (CDCl₃) δ 2.33 (s, 3H),4.81 (s, 2H), 6.74 (dd, J=2; 8 Hz, 1H), 7.04 (d, J=8 Hz, 1H), 7.12(d,J=2 Hz, 1H), 7.17-7.25 (m, 4H), 7.80(d, J=8 Hz, 2H). MS (FAB): m/e400(M+Li). Anal. Calc'd for C₁₉ H₁₄ F₂ ClNO₂ S: C, 57.95; H, 3.58; N,3.56.

Found: C, 57.91; H, 3.55; N, 3.54.

EXAMPLE 30 ##STR45##

Following the general procedure outlined in Synthetic Scheme XI, 2.50 g(5.93 mmol) of 2-chloro-4- 4,5-difluoro-2- 4-(methylsulfonyl)phenyl!phenyl!-N,N-dimethylbenzenamine (the title compound of Example28) was converted to its corresponding sulfonamide. Purification bysilica gel chromatography (MPLC) with ethyl acetate/hexane (3:7) gave1.75 g (70%) of 4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamideas a colorless solid: mp 193.0°-194.0° C.; NMR (CDCl₃) δ 2.83 (s, 6H),4.80 (s, 2H), 6.79 (dd, J=2, 9 Hz, 1H), 6.87-6.95 (m, 1H), 7.13(d, J=2Hz, 1H), 7.17-7.29 (m, 4H), 7.82(d, J=8 Hz, 2H). MS (0.27 H₂ O): C,56.16; H, 4.13; N, 6.55. Found: C, 56.16; H, 4.02; N, 6.39.

BIOLOGICAL EVALUATION

Rat Carrageenan Foot Pad Edema Test

The carrageenan foot edema test was performed with materials, reagentsand procedures essentially as described by Winter, et al., (Proc. Sec.Exp. Biol. Med., 111, 544 (1962)). Male Sprague-Dawley rats wereselected in each group so that the average body weight was as close aspossible. Rats were fasted with free access to water for over sixteenhours prior to the test. The rats were dosed orally (1 mL) withcompounds suspended in vehicle containing 0.5% methylcellulose and0.025% surfactant, or with vehicle alone. One hour later a supplanterinjection of 0.1 mL of 1% solution of carrageenan/sterile 0.9% salinewas administered and the volume of the injected foot was measured with adisplacement plethysmometer connected to a pressure transducer with adigital indicator. Three hours after the injection of the carrageenan,the volume of the foot was again measured. The average foot swelling ina group of drug-treated animals was compared with that of a group ofplacebo-treated animals and the percentage inhibition of edema wasdetermined (Otterness and Bliven, Laboratory Models for Testing NSAIDs,in Non-steroidal Anti-Inflammatory Drugs, (J. Lombardino, ed. 1985)).The % inhibition shows the % decrease from control paw volume determinedin this procedure and the data for selected compounds in this inventionare summarized in Table I.

Rat Carrageenan-induced Analgesia Test

The analgesia test using rat carrageenan was performed with materials,reagents and procedures essentially as described by Hargreaves, et al.,(Pain, 32, 77 (1988)). Male Sprague-Dawley rats were treated aspreviously described for the Carrageenan Foot Pad Edema test. Threehours after the injection of the carrageenan, the rats were placed in aspecial plexiglass container with a transparent floor having a highintensity lamp as a radiant heat source; positionable under the floor.After an initial twenty minute period, thermal stimulation was begun oneither the injected foot or on the contralateral uninjected foot. Aphotoelectric cell turned off the lamp and timer when light wasinterrupted by paw withdrawal. The time until the rat withdraws its footwas then measured. The withdrawal latency in seconds was determined forthe control and drug-treated groups, and percent inhibition of thehyperalgesic foot withdrawal determined. Results are shown in Table I.

                  TABLE I                                                         ______________________________________                                                 RAT PAW EDEMA    ANALGESIA                                                    % Inhibition @   % Inhibition @                                      Examples 10 mg/kg body weight                                                                           30 mg/kg body weight                                ______________________________________                                        1        26               ND                                                  2         6               28                                                  3        14                1                                                  20       19                22*                                                ______________________________________                                         *Assay performed at 50 mg/kg body weight                                 

Evaluation of COX I and COX II Activity In Vitro

The compounds of this invention exhibited inhibition in vitro of COX lI.The COX II inhibition activity of the compounds of this inventionillustrated in the Examples was determined by the following methods.

a. Preparation of Recombinant COX Baculoviruses

A 2.0 kb fragment containing the coding region of either human or murineCOX-I or human or murine COX-II was cloned into a BamH1 site of thebaculovirus transfer vector pVL1393-(Invitrogen) to generate thebaculovirus transfer vectors for COX-I and COX-II in a manner similar tothe method of D. R. O'Reilly et al (Baculovirus Expression Vectors: ALaboratory Manual (1992)). Recombinant baculoviruses were isolated bytransfecting 4 μg of baculovirus transfer vector DNA into SF9 insectcells (2×10e8) along with 200 ng of linearized baculovirus plasmid DNAby the calcium phosphate method. See M.D. Summers and G. E. Smith, AManual of Methods for Baculovirus Vectors and Insect Cell CultureProcedures, Texas Agric. Exp. Station Bull. 1555 (1987). Recombinantviruses were purified by three rounds of plaque purification and hightiter (10E7-10E8 pfu/ml) stocks of virus were prepared. For large scaleproduction, SF9 insect cells were infected in 10 liter fermentors(0.5×10⁶ /ml) with the recombinant baculovirus stock such that themultiplicity of infection was 0.1. After 72 hours the cells werecentrifuged and the cell pellet homogenized in Tris/Sucrose (50 mM: 25%,pH 8.0) containing 1% 3-(3-cholamidopropyl)dimethylammonio!-1-propanesulfonate (CHAPS). Thehomogenate was centrifuged at 10,000×G for 30 minutes, and the resultantsupernatant was stored at -80° C. before being assayed for COX activity.

b. Assay for COX I and COX II activity:

COX activity was assayed as PGE₂ formed/μg protein/time using an ELISAto detect the prostaglandin released. CHAPS-solubilized insect cellmembranes containing the appropriate COX enzyme were incubated in apotassium phosphate buffer (50 mM, pH 8.0) containing epinephrine,phenol, and heme with the addition of arachidonic acid (10 μM).Compounds were pre-incubated with the enzyme for 10-20 minutes prior tothe addition of arachidonic acid. Any reaction between the arachidonicacid and the enzyme was stopped after ten minutes at 37° C./roomtemperature by transferring 40 μl of reaction mix into 160 μl ELISAbuffer and 25 μM indomethacin. The PGE₂ formed was measured by standardELISA technology (Cayman Chemical). Results are shown in Table II.

                  TABLE II                                                        ______________________________________                                                     Human COX II                                                                             Human COX I                                           Example      ID.sub.50 μM                                                                          ID.sub.50 μM                                       ______________________________________                                        1            .3         >100                                                  2            <.1        19                                                    3            <.1        3.9                                                   4            >100       >100                                                  5            11.4       >100                                                  6            <.1        13.1                                                  7            <.1        8.2                                                   8            .1         >100                                                  9            2.8        32.6                                                  10           .4         >100                                                  11           <.1        >100                                                  12           <.1        9.2                                                   13           <.1        5.7                                                   14           <.1        >100                                                  15           7.2        >100                                                  16           <.1        5.5                                                   17           <.1        >100                                                  18           <.1        >100                                                  19           <.1        >100                                                  20           <.1        18.9                                                  21           <.1        22.5                                                  22           <.1        5.3                                                   23           <.1        >100                                                  24           <.1        >100                                                  25           <.1        17.0                                                  26           <.1        1.7                                                   27           <.1        >100                                                  28           <.1        >100                                                  29           <.1        16.5                                                  30           <.1        .6                                                    ______________________________________                                    

Also embraced within this invention is a class of pharmaceuticalcompositions comprising one or more compounds of Formula I inassociation with one or more non-toxic, pharmaceutically acceptablecarriers and/or diluents and/or adjuvants (collectively referred toherein as "carrier" materials) and, if desired, other activeingredients. The compounds of the present invention may be administeredby any suitable route, preferably in the form of a pharmaceuticalcomposition adapted to such a route, and in a dose effective for thetreatment intended. The compounds and composition mayi for example; beadministered intravascularly, intraperitoneally, subcutaneously,intramuscularly or topically.

For oral administration, the pharmaceutical composition may be in theform of, for example, a tablet, capsule, suspension or liquid. Thepharmaceutical composition is preferably made in the form of a dosageunit containing a particular amount of the active ingredient. Examplesof such dosage units are tablets or capsules. The active ingredient mayalso be administered by injection as a composition wherein, for example,saline; dextrose or water may be used as a suitable carrier.

The amount of therapeutically active compound that is administered andthe dosage regimen for treating a disease condition with the compoundsand/or compositions of this invention depends on a variety of factors,including the age, weight, sex and medical condition of the subject, theseverity of the disease, the route and frequency of administration, andthe particular compound employed, and thus may vary widely. Thepharmaceutical compositions may contain active ingredient in the rangeof about 0.1 to 2000 mg, preferably in the range of about 0.5 to 500 mgand most preferably between about 1 and 100 mg. A daily dose of about0.01 to 100 mg/kg body weight, preferably between about 0.1 and about 50mg/kg body weight and most preferably from about 1 to 20 mg/kg bodyweight, may be appropriate. The daily dose can be administered in one tofour doses per day.

For therapeutic purposes, the compounds of this invention are ordinarilycombined with one or more adjuvants appropriate to the indicated routeof administration. If administered per os, the compounds may be admixedwith lactose, sucrose; starch powder, cellulose esters of alkanoicacids, cellulose alkyl esters, talc, stearic acid, magnesium stearate;magnesium oxide, sodium and calcium salts of phosphoric and sulfuricacids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone;and/or polyvinyl alcohol, and then tableted or encapsulated forconvenient administration. Such capsules or tablets may contain acontrolled-release formulation as may be provided in a dispersion ofactive compound in hydroxypropylmethyl cellulose. Formulations forparenteral administration may be in the form of aqueous or non-aqueousisotonic sterile injection solutions or suspensions. These solutions andsuspensions may be prepared from sterile powders or granules having oneor more of the carriers or diluents mentioned for use in theformulations for oral administration. The compounds may be dissolved inwater, polyethylene glycol, propylene glycol, ethanol, corn oil,cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride,and/or various buffers. Other adjuvants and modes of administration arewell and widely known in the pharmaceutical art.

Although this invention has been described with respect to specificembodiments, the details of these embodiments are not to be construed aslimitations.

What is claimed is:
 1. A compound of Formula I ##STR46## wherein each ofR¹ through R⁴ is independently selected from the group consisting ofhydrido, halo, and alkoxy; wherein each of R⁵ through R¹⁴ isindependently selected from the group consisting of hydrido, alkyl,halo, alkoxy, alkylthio, cyano, haloalkyl, amino, alkylamino,dialkylamino, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto,aminosulfonyl and alkylsulfonyl; provided R¹² is selected from the groupconsisting of methylsulfonyl or aminosulfonyl; or apharmaceutically-acceptable salt thereof.
 2. A compound of Formula I##STR47## wherein each of R¹ through R⁴ is independently selected fromthe group consisting of hydrido and halo; or wherein R² and R³ togetherform --OCH₂ O--; wherein each of R⁵ through R⁸ is independently selectedfrom the group consisting of hydrido, lower alkyl, halo, lower alkoxy,lower haloalkyl, and lower dialkylamino; or wherein R⁶ and R⁷ togetherform --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and whereinR¹² is selected from the group consisting of aminosulfonyl andmethylsulfonyl; or a pharmaceutically-acceptable salt thereof.
 3. Apharmaceutical composition comprising a therapeutically-effective amountof a compound and a pharmaceutically-acceptable carrier or diluent, saidcompound selected from a family of compounds of Formula I ##STR48##wherein each of R¹ through R⁴ is independently selected from the groupconsisting of hydrido and halo; or wherein R² and R together form --OCH₂O--; wherein each of R⁵ through R⁸ is independently selected from thegroup consisting of hydrido, lower alkyl, halo, lower alkoxy, lowerhaloalkyl, and lower dialkylamino; or wherein R⁶ and R⁷ together form--OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and wherein R¹²is selected from the group consisting of aminosulfonyl andmethylsulfonyl; or a pharmaceutically-acceptable salt thereof. 4.Compound of claim 2 wherein each of R¹ through R⁴ is independentlyselected from the group consisting of hydrido and halo; or wherein R²and R³ together form --OCH₂ O--; wherein each of R⁵ and R⁹ is hydrido;wherein each of R⁶ through R⁸ is independently selected from the groupconsisting of hydrido, lower alkyl, halo, lower alkoxy, lower haloalkyl,and lower dialkylamino; or wherein R⁶ and R⁷ together form --OCH₂ O--;wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and wherein R¹² isaminosulfonyl; or a pharmaceutically-acceptable salt thereof. 5.Compound of claim 4 wherein each of R¹ through R⁴ is independentlyselected from the group consisting of hydrido, fluoror, chloro andbromo; or wherein R² and R³ together form --OCH₂ O--; wherein each of R⁵and R⁹ is hydrido; wherein each of R⁶ through R⁸ is independentlyselected from the group consisting of hydrido, methyl, ethyl, fluoro,chloro, bromo, methoxy, ethoxy, propoxy, n-butoxy, fluoromethyl,difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl,trichloromethyl, pentafluoroethyl, heptafluoropropyl,difluorochloromethyl, dichlorofluoromethyl, difluoroethyl,difluoropropyl, dichloroethyl, dichloropropyl, N-ethyl-N-methylamino,N,N-dimethylamino, and N,N-diethylamino; or wherein R⁶ and R⁷ togetherform --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and whereinR¹² is aminosulfonyl; or a pharmaceutically-acceptable salt thereof. 6.Compound of claim 5 selected from compounds, and their pharmaceuticallyacceptable salts, of the group consisting of4-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chloro-3-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,4-dichlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4- 2-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4- 2-3-fluoro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-6-(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6-(3,4-difluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6-(3-chloro-4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6- 4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 6-4-(N,N-dimethylamino)-3-fluorophenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 6-3-chloro-4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-difluoro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-dichloro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-difluoro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide4-6(3,5-dichloro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 4,5-difluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluoro-3-methylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluoro-3-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(3,4-dichlorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2- 4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-methylphenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-4-(N,N-dimethylamino)-3-fluorophenyl!phenyl!benzenesulfonamide; 4- 2-3-chloro-4-N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-methoxyphenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,4,5-trimethylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,5-difluoro-4-methylphenyl)phenyl!benzenesulfonamide;4-2-(3,5-dichloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethoxy-4-methylphenyl)phenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethyl-4-methoxyphenyl)phenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-difluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;4-2-(3,5-dichloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-(3,4,5-trimethoxyphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,5-dimethyl-4-fluorophenyl)phenyl!benzenesulfonamide;4- 4,5-difluoro-2-(3,4,5-trifluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,5-dichloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethoxy-4-fluorophenyl)phenyl!benzenesulfonamide;4-2-(4-chloro-3,5-dimethylphenyl)-4,5-difluorophenyl!benzenesulfonamide;4-2-(4-chloro-3,5-difluorophenyl)-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-(3,4,5-trichlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chloro-3,5-dimethoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;4,5-difluoro-2-3,5-dimethyl-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-3,5-difluoro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-2-3,5-dichloro-4-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-methylphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-methoxy-3-methylphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(3,4-dimethoxyphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-fluoro-3-methylphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide;and 4-2,3,4,5-tetrafluoro-2-(4-fluoro-3-methoxyphenyl)phenyl!benzenesulfonamide.7. Compound of claim 5 selected from compounds, and theirpharmaceutically acceptable salts, of the group consisting of4-2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-a-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-6(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-4,5-difluoro-2-4-(methylphenyl)phenyl!benzenesulfonamide; 4-2-(1,3-benzodioxol-5-yl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; and4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide.8. Compound of claim 5 where the compound is 4-4,5-difluoro-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide, or apharmaceutically-acceptable salt thereof.
 9. Compound of claim 5 wherethe compound is 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide, or apharmaceutically-acceptable salt thereof.
 10. Compound of claim 2wherein each of R¹ and R⁴ are hydrido; wherein each of R² and R³ isindependently selected from the group consisting of hydrido and halo; orwherein R² and R³ together form --OCH₂ O--; wherein each of R⁵ and R⁹ ishydrido; wherein each of R⁶ through R⁸ is independently selected fromthe group consisting of hydrido, lower alkyl, halo, and lower alkoxy; orwherein R⁶ and R⁷ together form --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ andR¹⁴ are hydrido; and wherein R¹² is methylsulfonyl; or apharmaceutically-acceptable salt thereof.
 11. Compound of claim 10wherein each of R¹ and R⁴ are hydrido; wherein each of R² and R³ isindependently selected from the group consisting of hydrido, fluoro,chloro and bromo; or wherein R² and R³ together form --OCH₂ O--; whereineach of R⁵ and R⁹ is hydrido; wherein each of R⁶ through R⁸ isindependently selected from the group consisting of hydrido, methyl,ethyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy, and n-butoxy; orwherein R⁶ and R⁷ together form --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ andR¹⁴ are hydrido; and wherein R¹² is methylsulfonyl; or apharmaceutically-acceptable salt thereof.
 12. Compound of claim 11selected from compounds, and their pharmaceutically acceptable salts, ofthe group consisting of1-(4-fluorophenyl)-2-4-(methylsulfonyl)phenyl!benzene; 1-(4-chlorophenyl)-2-4-(methylsulfonyl)phenyl!benzene; 1-(3-chloro-4-methoxyphenyl)-2-4-(methylsulfonyl)phenyl!benzene; 1-(3-fluoro-4-methoxyphenyl)-2-4-(methylsulfonyl)phenyl!benzene; 1-(3-chloro-4-fluorophenyl)-2-4-(methylsulfonyl)phenyl!benzene; 1-(4-fluorophenyl)-6-4-(methylsulfonyl)phenyl!-1,3-benzodioxole;1,2-difluoro-4-(4-fluorophenyl)-5- 4-(methylsulfonyl)phenyl!benzene;1,2-difluoro-4-(4-methylphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1,2-difluoro-4-(3-fluoro-4-methoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1-(3,5-dichloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1-(3,5-difluoro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene; 5- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-1,3-benzodioxole;1-(3-chloro-4-methylphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene; and 2-chloro-4- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-N,N-dimethylbenzeneamine.
 13. Acompound of Formula II ##STR49## wherein each of R² and R³ isindependently selected from the group consisting of hydrido and halo; orwherein R² and R³ together form --OCH₂ O--; wherein each of R⁶ throughR⁸ is independently selected from the group consisting of hydrido, loweralkyl, halo, lower alkoxy, lower haloalkyl, and lower dialkylamino; orwherein R⁶ and R⁷ together form --OCH₂ O--; and wherein R¹² is selectedfrom the group consisting of lower alkylsulfonyl and aminosulfonyl; or apharmaceutically-acceptable salt thereof.
 14. A compound of Formula III##STR50## wherein each of R⁶ through R⁸ is independently selected fromhydrido, halo, lower alkoxy, lower haloalkyl, amino, lower alkylamino,lower dialkylamino, and lower haloalkoxy; or wherein R⁶ and R⁷ togetherform --OCH₂ O--; or a pharmaceutically-acceptable salt thereof.
 15. Apharmaceutical composition comprising a therapeutically-effective amountof a compound and a pharmaceutically-acceptable carrier or diluent, saidcompound selected from a family of compounds of Formula I ##STR51##wherein each of R¹ through R⁴ is independently selected from the groupconsisting of hydrido, halo, and alkoxy; wherein each of R⁵ through R¹⁴is independently selected from the group consisting of hydrido, alkyl,halo, alkoxy, alkylthio, cyano, haloalkyl, amino, alkylamino,dialkylamino, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto,aminosulfonyl and alkylsulfonyl; provided R¹² is selected from the groupconsisting of methylsulfonyl or aminosulfonyl; or apharmaceutically-acceptable salt thereof.
 16. The composition of claim15 wherein each of R¹ through R⁴ is independently selected from thegroup consisting of hydrido and halo; or wherein R² and R³ together form--OCH₂ O--; and wherein each of R⁵ through R¹⁴ is independently selectedfrom the group consisting of hydrido, lower alkyl, halo, lower alkoxy,lower alkylthio, cyano, lower haloalkyl, amino, lower alkylamino, lowerdialkylamino, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl,hydroxyl, mercapto, aminosulfonyl and lower alkylsulfonyl; or wherein R⁶and R⁷ together form --OCH₂ O--; provided R¹² is selected from the groupconsisting of methylsulfonyl or aminosulfonyl; or apharmaceutically-acceptable salt thereof.
 17. The composition of claim16 wherein each of R¹ through R.sup. 4 is independently selected fromthe group consisting of hydrido and halo; or wherein R² and R³ togetherform --OCH₂ O--; wherein each of R⁵ through R⁸ is independently selectedfrom the group, consisting of hydrido, lower alkyl, halo, lower alkoxy,lower haloalkyl, and lower dialkylamino; or wherein R⁶ and R⁷ togetherform --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and whereinR¹² is selected from the group consisting of aminosulfonyl and loweralkylsulfonyl; or a pharmaceutically-acceptable salt thereof.
 18. Thecomposition of claim 17 wherein each of R¹ through R⁴ is independentlyselected from hydrido and halo; or wherein R² and R³ together form--OCH₂ O--; wherein each of R⁵ and R⁹ is hydrido; wherein each of R⁶through R⁸ is independently selected from hydrido, lower alkyl, halo,lower alkoxy, lower haloalkyl, and lower dialkylamino; or wherein R⁶ andR⁷ together form --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido;and wherein R¹² is aminosulfonyl; or a pharmaceutically-acceptable saltthereof.
 19. The composition of claim 18 wherein each of R¹ through R⁴is independently selected from hydrido, fluoro, chloro and bromo; orwherein R² and R³ together form --OCH₂ O--; wherein each of R⁵ and R⁹ ishydrido; wherein each of R⁶ through R⁸ is independently selected fromhydrido, methyl, ethyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy,n-butoxy, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl,difluorochloromethyl, dichlorofluoromethyl, difluoroethyl,difluoropropyl, dichloroethyl, dichloropropyl, N-ethyl-N-methylamino,N,N-dimethylamino, and N,N-diethylamino; or wherein R⁶ and R⁷ togetherform --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and whereinR¹² is aminosulfonyl; or a pharmaceutically-acceptable salt thereof. 20.The composition of claim 19 wherein said compound is selected fromcompounds, and their pharmaceutically acceptable salts, of the groupconsisting of4- 2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chloro-3-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,4-dichlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-atrifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4- 2-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4- 2-3-fluoro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-6-(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6-(3,4-difluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6-(3-chloro-4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6- 4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 6-4-(N,N-dimethylamino)-3-fluorophenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 6-3-chloro-4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-difluoro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-dichloro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-difluoro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide);4-6-(3,5-dichloro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 4,5-difluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluoro-3-methylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluoro-3-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(3,4-dichlorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2- 4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-methylphenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-4-(N,N-dimethylamino)-3-fluorophenyl!phenyl!benzenesulfonamide; 4- 2-3-chloro-4-N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-methoxyphenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,4,5-trimethylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,5-difluoro-4-methylphenyl)phenyl!benzenesulfonamide;4-2-(3,5-dichloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethoxy-4-methylphenyl)phenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethyl-4-methoxyphenyl)phenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-difluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;4-2-(3,5-dichloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-(3,4,5-trimethoxyphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,5-dimethyl-4-fluorophenyl)phenyl!benzenesulfonamide;4- 4,5-difluoro-2-(3,4,5-trifluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,5-dichloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethoxy-4-fluorophenyl)phenyl!benzenesulfonamide;4-2-(4-chloro-3,5-dimethylphenyl)-4,5-difluorophenyl!benzenesulfonamide;4-2-(4-chloro-3,5-difluorophenyl)-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-(3,4,5-trichlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chloro-3,5-dimethoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-3,5-dimethyl-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-3,5-difluoro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-2-3,5-dichloro-4-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-methylphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-methoxy-3-methylphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(3,4-dimethoxyphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-fluoro-3-methylphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide;and 4-2,3,4,5-tetrafluoro-2-(4-fluoro-3-methoxyphenyl)phenyl!benzenesulfonamide.21. The composition of claim 19 wherein said compound is selected fromcompounds, and their pharmaceutically acceptable salts, of the groupconsisting of4-2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4- 6(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-4,5-difluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(1,3-benzodioxol-5-yl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; and4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide.22. The composition of claim 19 where the compound is 4-4,5-difluoro-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide, or apharmaceutically-acceptable salt thereof.
 23. The composition of claim19 where the compound is 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide, or apharmaceutically-acceptable salt thereof.
 24. The composition of claim17 wherein each of R¹ and R⁴ are hydrido; wherein each of R² and R³ isindependently selected from the group consisting of hydrido and halo; orwherein R² and R³ together form --OCH₂ O--; wherein each of R⁵ and R⁹ ishydrido; wherein each of R⁶ through R⁸ is independently selected fromthe group consisting of hydrido, lower alkyl, halo, and lower alkoxy; orwherein R⁶ and R⁷ together form --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ andR¹⁴ are hydrido; and wherein R¹² is lower alkylsulfonyl; or apharmaceutically-acceptable salt thereof.
 25. The composition of claim24 wherein each of R¹ and R⁴ are hydrido; wherein each of R² and R³ isindependently selected from the group consisting of hydrido, fluoro,chloro and bromo; or wherein R² and R³ together form --OCH₂ O--; whereineach of R⁵ and R⁹ is hydrido; wherein each of R⁶ through R⁸ isindependently selected from the group consisting of hydrido, methyl,ethyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy, and n-butoxy; orwherein R⁶ and R⁷ together form --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ andR¹⁴ are hydrido; and wherein R¹² is methylsulfonyl; or apharmaceutically-acceptable salt thereof.
 26. The composition of claim25 wherein said compound is selected from compounds, and theirpharmaceutically acceptable salts of the group consistingof1-(4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(4-chlorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(3-fluoro-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-4-fluorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;1,2-difluoro-4-(4-fluorophenyl)-5- 4-(methylsulfonyl)phenyl!benzene;1,2-difluoro-4-(4-methylphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;1-3-chloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1,2-difluoro-4-(3-fluoro-4-methoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1-(3,5-dichloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1-(3,5-difluoro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene; 5- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-1,3-benzodioxole;1-(3-chloro-4-methylphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene; and 2-chloro-4- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-N,N-dimethylbenzeneamine.
 27. Apharmaceutical composition comprising a therapeutically-effective amountof a compound and a pharmaceutically-acceptable carrier or diluent, saidcompound selected from a family of compounds of Formula II ##STR52##wherein each of R² and R³ is independently selected from the groupconsisting of hydrido and halo; or wherein R² and R³ together form--OCH₂ O--; wherein each of R⁶ through R⁸ is independently selected fromthe, group consisting of hydrido, lower alkyl, halo, lower alkoxy, lowerhaloalkyl, and lower dialkylamino; or wherein R⁶ and R⁷ together form--OCH₂ O--; and wherein R¹² is selected from the group consisting oflower alkylsulfonyl and aminosulfonyl; or a pharmaceutically-acceptablesalt thereof.
 28. A pharmaceutical composition comprising atherapeutically-effective amount of a compound and apharmaceutically-acceptable carrier or diluent, said compound selectedfrom a family of compounds of Formula III ##STR53## wherein each of R⁶through R⁸ is independently selected from hydrido, halo, lower alkoxy,lower haloalkyl, amino, lower alkylamino, lower dialkylamino, and lowerhaloalkoxy; or wherein R⁶ and R⁷ together form --OCH₂ O--; or apharmaceutically-acceptable salt thereof.
 29. A method of treatinginflammation or an inflammation-associated disorder in a subject, saidmethod comprising administering to the subject having or susceptible tosuch inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of Formula I ##STR54##wherein each of R¹ through R⁴ is independently selected from the groupconsisting of hydrido, halo, and alkoxy; wherein each of R⁵ through R¹⁴is independently selected from the group consisting of hydrido, alkyl,halo, alkoxy, alkylthio, cyano, haloalkyl, amino, alkylamino,dialkylamino, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto,aminosulfonyl and alkylsulfonyl; or a pharmaceutically-acceptable saltthereof.
 30. The method of claim 29 wherein each of R¹ through R⁴ isindependently selected from the group consisting of hydrido and halo; orwherein R² and R³ together form --OCH₂ O--; and wherein each of R⁵through R¹⁴ is independently selected from the group consisting ofhydrido, lower alkyl, halo, lower alkoxy, lower alkylthio, cyano, lowerhaloalkyl, amino, lower alkylamino, lower dialkylamino, lowerhaloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl, mercapto,aminosulfonyl and lower alkylsulfonyl; or wherein R⁶ and R⁷ togetherform --OCH₂ O--; or a pharmaceutically-acceptable salt thereof.
 31. Themethod of claim 30 wherein each of R¹ through R⁴ is independentlyselected from hydrido and halo; or wherein R² and R³ together form--OCH₂ O--; wherein each of R⁵ through R⁸ is independently selected fromthe group consisting of hydrido, lower alkyl, halo, lower alkoxy, lowerhaloalkyl, and lower dialkylamino; or wherein R⁶ and R⁷ together form--OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and wherein R¹²is selected from the group consisting of aminosulfonyl and loweralkylsulfonyl; or a pharmaceutically-acceptable salt thereof.
 32. Themethod of claim 31 wherein each of R¹ through R⁴ is independentlyselected from the group consisting of hydrido and halo; or wherein R²and R³ together form --OCH₂ O--; wherein each of R⁵ and R⁹ is hydrido;wherein each of R⁶ through R⁸ is independently selected from the groupconsisting of hydrido, lower alkyl, halo, lower alkoxy, lower haloalkyl,and lower dialkylamino; or wherein R⁶ and R⁷ together form --OCH₂ O--;wherein R¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and wherein R¹² isaminosulfonyl; or a pharmaceutically-acceptable salt thereof.
 33. Themethod of claim 32 wherein each of R¹ through R⁴ is independentlyselected from the group consisting of hydrido, fluoro, chloro and bromo;or wherein R² and R³ together form --OCH₂ O--; wherein each of R⁵ and R⁹is hydrido; wherein each of R⁶ through R⁸ is independently selected fromthe group consisting of hydrido, methyl, ethyl, fluoro, chloro, bromo,methoxy, ethoxy, propoxy, n-butoxy, fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl,dichloropropyl, N-ethyl-N-methylamino, N,N-dimethylamino, andN,N-diethyiamino; or wherein R⁶ and R⁷ together form --OCH₂ O--; whereinR¹⁰, R¹¹, R¹³ and R¹⁴ are hydrido; and wherein R¹² is aminosulfonyl; ora pharmaceutically-acceptable salt thereof.
 34. The method of claim 33wherein said compound is selected from compounds, and theirpharmaceutically acceptable salts, of the group consisting of4-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chloro-3-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,4-dichlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4- 2-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4- 2-3-fluoro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-6-(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6-(3,4-difluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6-(3-chloro-4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6- 4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 6-4-(N,N-dimethylamino)-3-fluorophenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 6- 3-chloro-4-(N,N-dimethylamino)phenyl!-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-6-(3,5-difluoro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-dichloro-4-methylphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-difluoro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4-6-(3,5-dichloro-4-methoxyphenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide;4- 4,5-difluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluoro-3-methylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluoro-3-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(3,4-dichlorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-chloro-3-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2- 4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide;4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-methylphenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-4-(N,N-dimethylamino)-3-fluorophenyl!phenyl!benzenesulfonamide; 4- 2-3-chloro-4-N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-4-(N,N-dimethylamino)-3-methoxyphenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,4,5-trimethylphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,5-difluoro-4-methylphenyl)phenyl!benzenesulfonamide;4-2-(3,5-dichloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethoxy-4-methylphenyl)phenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethyl-4-methoxyphenyl)phenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-difluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;4-2-(3,5-dichloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-(3,4,5-trimethoxyphenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,5-dimethyl-4-fluorophenyl)phenyl!benzenesulfonamide;4- 4,5-difluoro-2-(3,4,5-trifluorophenyl)phenyl!benzenesulfonamide; 4-2-(3,5-dichloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide;4-4,5-difluoro-2-(3,5-dimethoxy-4-fluorophenyl)phenyl!benzenesulfonamide;4-2-(4-chloro-3,5-dimethylphenyl)-4,5-difluorophenyl!benzenesulfonamide;4- 2-(4-chloro-3,5-difluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3,4,5-trichlorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chloro-3,5-dimethoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide;4- 4,5-difluoro-2-3,5-dimethyl-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-4,5-difluoro-2-3,5-difluoro-4-(N,N-dimethylamino)phenyl!phenyl!benzenesulfonamide; 4-2-3,5-dichloro-4-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(3-fluoro-4-methylphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-methylphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-methoxy-3-methylphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(3,4-dimethoxyphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-fluoro-3-methylphenyl)phenyl!benzenesulfonamide;4- 2,3,4,5-tetrafluoro-2-(3,4-difluorophenyl)phenyl!benzenesulfonamide;4-2,3,4,5-tetrafluoro-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide;and 4-2,3,4,5-tetrafluoro-2-(4-fluoro-3-methoxyphenyl)phenyl!benzenesulfonamide.35. The method of claim 33 wherein said compound is selected fromcompounds, and their pharmaceutically acceptable salts, of the groupconsisting of4- 2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(4-chlorophenyl)phenyl!benzenesulfonamide; 4-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-2-(4-trifluoromethylphenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide; 4-4,5-difluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2,3,4,5-tetrafluoro-2-(4-fluorophenyl)phenyl!benzenesulfonamide; 4-2-(3-chloro-4-methoxyphenyl)-4,5-difluorophenyl!benzenesulfonamide; 4-4,5-difluoro-2-(3-fluoro-4-methoxyphenyl)phenyl!benzenesulfonamide; 4-6-(4-fluorophenyl)-1,3-benzodioxol-5-yl!benzenesulfonamide; 4-4,5-difluoro-2-(4-methylphenyl)phenyl!benzenesulfonamide; 4-2-(1,3-benzodioxol-5-yl)-4,5-difluorophenyl!benzenesulfonamide; 4-2-(3-chloro-4-methylphenyl)-4,5-difluorophenyl!benzenesulfonamide; and4- 2-3-chloro-4-(N,N-dimethylamino)phenyl!-4,5-difluorophenyl!benzenesulfonamide.36. The method of claim 33 where the compound is 4-4,5-difluoro-2-(3-chloro-4-fluorophenyl)phenyl!benzenesulfonamide, or apharmaceutically-acceptable salt thereof.
 37. The method of claim 33where the compound is 4-2-(3-chloro-4-methoxyphenyl)phenyl!benzenesulfonamide, or apharmaceutically-acceptable salt thereof.
 38. The method of claim 31wherein each of R¹ and R⁴ are hydrido; wherein each of R² and R³ isindependently selected from the group consisting of hydrido and halo; orwherein R² and R³ together form --OCH₂ O--; wherein each of R⁵ and R⁹ ishydrido; wherein each of R⁶ through R⁸ is independently selected fromthe group consisting of hydrido, lower alkyl, halo, and lower alkoxy; orwherein R⁶ and R⁷ together form --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ andR¹⁴ are hydrido; and wherein R¹² is lower alkylsulfonyl; or apharmaceutically-acceptable salt thereof.
 39. The method of claim 38wherein each of R¹ and R⁴ are hydrido; wherein each of R² and R³ isindependently selected from the group consisting of hydrido, fluoro,chloro and bromo; or wherein R² and R³ together form --OCH₂ O--; whereineach of R⁵ and R⁹ is hydrido; wherein each of R⁶ through R⁸ isindependently selected from the group consisting of hydrido, methyl,ethyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy, and n-butoxy; orwherein R⁶ and R⁷ together form --OCH₂ O--; wherein R¹⁰, R¹¹, R¹³ andR¹⁴ are hydrido; and wherein R¹² is methylsulfonyl; or apharmaceutically-acceptable salt thereof.
 40. The method of claim 39wherein said compound is selected from compounds, and theirpharmaceutically acceptable salts, of the group consistingof1-(4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(4-chlorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(3-fluoro-4-methoxyphenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-fluorophenyl)-2- 4-(methylsulfonyl)phenyl!benzene;1-(4-fluorophenyl)-6- 4-(methylsulfonyl)phenyl!-1,3-benzodioxole;1,2-difluoro-4-(4-fluorophenyl)-5- 4-(methylsulfonyl)phenyl!benzene;1,2-difluoro-4-(4-methylphenyl)-5- 4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1,2-difluoro-4-(3-fluoro-4-methoxyphenyl)-5-4-(methylsulfonyl)phenyl!benzene;1-(3,5-dichloro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1-(3,5-difluoro-4-methoxyphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene;1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene; 5- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-1,3-benzodioxole;1-(3-chloro-4-methylphenyl)-4,5-difluoro-2-4-(methylsulfonyl)phenyl!benzene; and 2-chloro-4- 4,5-difluoro-2-4-(methylsulfonyl)phenyl!phenyl!-N,N-dimethylbenzeneamine.
 41. A methodof treating inflammation or an inflammation-associated disorder in asubject, said method comprising administering to the subject having orsusceptible to such inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of Formula II ##STR55##wherein each of R² and R³ is independently selected from the groupconsisting of hydrido and halo; or wherein R² and R³ together form--OCH₂ O--; wherein each of R⁶ through R⁸ is independently selected fromthe group consisting of hydrido, lower alkyl, halo, lower alkoxy, lowerhaloalkyl, and lower dialkylamino; or wherein R⁶ and R⁷ together form--OCH₂ O--; and wherein R¹² is selected from the group consisting oflower alkylsulfonyl and aminosulfonyl; or a pharmaceutically-acceptablesalt thereof.
 42. A method of treating inflammation or aninflammation-associated disorder in a subject, said method comprisingadministering to the subject having or susceptible to such inflammationor inflammation-associated disorder, a therapeutically-effective amountof a compound of Formula III ##STR56## wherein each of R⁶ through R⁸ isindependently selected from the group consisting of hydrido, halo, loweralkoxy, lower haloalkyl, amino, lower alkylamino, lower dialkylamino,and lower haloalkoxy; or wherein R⁶ and R⁷ together form --OCH₂ O--; ora pharmaceutically-acceptable salt thereof.
 43. The method of claim 29for use in treatment of inflammation.
 44. The method of claim 29 for usein treatment of an inflammation-associated disorder.
 45. The method ofclaim 44 wherein the inflammation-associated disorder is arthritis. 46.The method of claim 44 wherein the inflammation-associated disorder ispain.
 47. The method of claim 44 wherein the inflammation-associateddisorder is fever.